Pub Date : 2024-09-19DOI: 10.1038/s12276-024-01320-0
Hyondeog Kim, Wonyeop Lee, Youngwook Kim, Sang-Jin Lee, Wonyoung Choi, Geon Kook Lee, Seung-Jin Park, Shinyeong Ju, Seon-Young Kim, Cheolju Lee, Ji-Youn Han
Patients with lung adenocarcinoma who have never smoked (NSLA) and lack key driver mutations, such as those in the EGFR and ALK genes, face limited options for targeted therapies. They also tend to have poorer outcomes with immune checkpoint inhibitors than lung cancer patients who have a history of smoking. The proteogenomic profile of nonsmoking lung adenocarcinoma patients without these oncogenic driver mutations is poorly understood, which complicates the precise molecular classification of these cancers and highlights a significant area of unmet clinical need. This study analyzed the genome, transcriptome, and LC‒MS/MS-TMT-driven proteome data of tumors obtained from 99 Korean never-smoker lung adenocarcinoma patients. NSLA tumors without EGFR or ALK driver oncogenes were classified into four proteogenomic subgroups: proliferation, angiogenesis, immune, and metabolism subgroups. These 4 molecular subgroups were strongly associated with distinct clinical outcomes. The proliferation and angiogenesis subtypes were associated with a poorer prognosis, while the immune subtype was associated with the most favorable outcome, which was validated in an external lung cancer dataset. Genomic-wide impacts were analyzed, and significant correlations were found between copy number alterations and both the transcriptome and proteome for several genes, with enrichment in the ERBB, neurotrophin, insulin, and MAPK signaling pathways. Proteogenomic analyses suggested several targetable genes and proteins, including CDKs and ATR, as potential therapeutic targets in the proliferation subgroup. Upregulated cytokines, such as CCL5 and CXCL13, in the immune subgroup may serve as potential targets for combination immunotherapy. Our comprehensive proteogenomic analysis revealed the molecular subtypes of EGFR- and ALK-wild-type NSLA with significant unmet clinical needs. Lung cancer is the leading cause of cancer deaths worldwide, with increasing cases in non-smokers, particularly Asian women. This research investigates lung adenocarcinoma in non-smokers who don’t have common genetic changes, using a multi-omics approach. The study involved 99 patients, specifically those without typical EGFR or ALK mutations, to better understand the disease at a molecular level and find new treatments. The study shows the variety within non-smoker lung cancers and suggests that different groups may need specific treatments. Understanding the molecular types of lung adenocarcinoma in non-smokers can lead to better, personalized treatments and improved health outcomes. This research could lead to more effective treatments for non-smoker lung cancer, potentially improving survival and quality of life for this growing patient group. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"Proteogenomic characterization identifies clinical subgroups in EGFR and ALK wild-type never-smoker lung adenocarcinoma","authors":"Hyondeog Kim, Wonyeop Lee, Youngwook Kim, Sang-Jin Lee, Wonyoung Choi, Geon Kook Lee, Seung-Jin Park, Shinyeong Ju, Seon-Young Kim, Cheolju Lee, Ji-Youn Han","doi":"10.1038/s12276-024-01320-0","DOIUrl":"10.1038/s12276-024-01320-0","url":null,"abstract":"Patients with lung adenocarcinoma who have never smoked (NSLA) and lack key driver mutations, such as those in the EGFR and ALK genes, face limited options for targeted therapies. They also tend to have poorer outcomes with immune checkpoint inhibitors than lung cancer patients who have a history of smoking. The proteogenomic profile of nonsmoking lung adenocarcinoma patients without these oncogenic driver mutations is poorly understood, which complicates the precise molecular classification of these cancers and highlights a significant area of unmet clinical need. This study analyzed the genome, transcriptome, and LC‒MS/MS-TMT-driven proteome data of tumors obtained from 99 Korean never-smoker lung adenocarcinoma patients. NSLA tumors without EGFR or ALK driver oncogenes were classified into four proteogenomic subgroups: proliferation, angiogenesis, immune, and metabolism subgroups. These 4 molecular subgroups were strongly associated with distinct clinical outcomes. The proliferation and angiogenesis subtypes were associated with a poorer prognosis, while the immune subtype was associated with the most favorable outcome, which was validated in an external lung cancer dataset. Genomic-wide impacts were analyzed, and significant correlations were found between copy number alterations and both the transcriptome and proteome for several genes, with enrichment in the ERBB, neurotrophin, insulin, and MAPK signaling pathways. Proteogenomic analyses suggested several targetable genes and proteins, including CDKs and ATR, as potential therapeutic targets in the proliferation subgroup. Upregulated cytokines, such as CCL5 and CXCL13, in the immune subgroup may serve as potential targets for combination immunotherapy. Our comprehensive proteogenomic analysis revealed the molecular subtypes of EGFR- and ALK-wild-type NSLA with significant unmet clinical needs. Lung cancer is the leading cause of cancer deaths worldwide, with increasing cases in non-smokers, particularly Asian women. This research investigates lung adenocarcinoma in non-smokers who don’t have common genetic changes, using a multi-omics approach. The study involved 99 patients, specifically those without typical EGFR or ALK mutations, to better understand the disease at a molecular level and find new treatments. The study shows the variety within non-smoker lung cancers and suggests that different groups may need specific treatments. Understanding the molecular types of lung adenocarcinoma in non-smokers can lead to better, personalized treatments and improved health outcomes. This research could lead to more effective treatments for non-smoker lung cancer, potentially improving survival and quality of life for this growing patient group. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01320-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1038/s12276-024-01300-4
Ji Min Park, Yen-Hao Su, Chi-Shuan Fan, Hsin-Hua Chen, Yuan-Kai Qiu, Li-Li Chen, Hsin-An Chen, Thamil Selvee Ramasamy, Jung-Su Chang, Shih-Yi Huang, Wun-Shaing Wayne Chang, Alan Yueh-Luen Lee, Tze-Sing Huang, Cheng-Chin Kuo, Ching-Feng Chiu
Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development. Iron storage in our body is mainly controlled by a protein named ferritin, which reflects the amount of stored iron through its blood levels. Low ferritin levels usually suggest iron-deficiency anemia, while high levels can indicate inflammation and hinting at ferritin’s potential as a cancer indicator. In this study, scientists focused on pancreatic cancer, notorious for its low survival rates and limited treatment options. They examined the expression of different ferritin components and their link with the KRAS mutation, a common characteristic in pancreatic cancer that promotes tumor growth. The main discovery is that high FTH1 expression is associated with worse survival in pancreatic cancer patients, suggesting that targeting FTH1 could be a promising treatment for this aggressive cancer. This study enhances our knowledge of the molecular processes driving pancreatic cancer and opens new paths for targeted treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"Crosstalk between FTH1 and PYCR1 dysregulates proline metabolism and mediates cell growth in KRAS-mutant pancreatic cancer cells","authors":"Ji Min Park, Yen-Hao Su, Chi-Shuan Fan, Hsin-Hua Chen, Yuan-Kai Qiu, Li-Li Chen, Hsin-An Chen, Thamil Selvee Ramasamy, Jung-Su Chang, Shih-Yi Huang, Wun-Shaing Wayne Chang, Alan Yueh-Luen Lee, Tze-Sing Huang, Cheng-Chin Kuo, Ching-Feng Chiu","doi":"10.1038/s12276-024-01300-4","DOIUrl":"10.1038/s12276-024-01300-4","url":null,"abstract":"Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development. Iron storage in our body is mainly controlled by a protein named ferritin, which reflects the amount of stored iron through its blood levels. Low ferritin levels usually suggest iron-deficiency anemia, while high levels can indicate inflammation and hinting at ferritin’s potential as a cancer indicator. In this study, scientists focused on pancreatic cancer, notorious for its low survival rates and limited treatment options. They examined the expression of different ferritin components and their link with the KRAS mutation, a common characteristic in pancreatic cancer that promotes tumor growth. The main discovery is that high FTH1 expression is associated with worse survival in pancreatic cancer patients, suggesting that targeting FTH1 could be a promising treatment for this aggressive cancer. This study enhances our knowledge of the molecular processes driving pancreatic cancer and opens new paths for targeted treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01300-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1038/s12276-024-01304-0
Hyang Hee Cho, Siyeon Rhee, Dong Im Cho, Ju Hee Jun, HyoJung Heo, Su Han Cho, Dohyup Kim, Mingqiang Wang, Bo Gyeong Kang, Soo Ji Yoo, Meeyoung Cho, Soo yeon Lim, Jae Yeong Cho, In Seok Jeong, Yong Sook Kim, Youngkeun Ahn
The regulatory role of the inhibitor of NF-kB kinase ε (IKKε) in postmyocardial infarction (MI) inflammation remains uncertain. Using an MI mouse model, we examined the cardiac outcomes of IKKε knockout (KO) mice and wild-type mice. We employed single-cell RNA sequencing (scRNA-seq) and phosphorylated protein array techniques to profile cardiac macrophages. IKKε KO mice exhibited compromised survival, heightened inflammation, pronounced cardiac fibrosis, and a reduced ejection fraction. A distinct cardiac macrophage subset in IKKε KO mice exhibited increased fibrotic marker expression and decreased phosphorylated p38 (p-p38) levels, indicating an enhanced macrophage–myofibroblast transition (MMT) post-MI. While cardiac inflammation is crucial for initiating compensatory pathways, the timely resolution of inflammation was impaired in the IKKε KO group, while the MMT in macrophages accelerated post-MI, leading to cardiac failure. Additionally, our study highlighted the potential of 5-azacytidine (5-Aza), known for its anti-inflammatory and cardioprotective effects, in restoring p-p38 levels in stimulated macrophages. The administration of 5-Aza significantly reduced the MMT in cardiac macrophages from the IKKε KO group. These findings underscore the regulation of the inflammatory response and macrophage transition by the IKKε-p38 axis, indicating that the MMT is a promising therapeutic target for ischemic heart disease. Heart attacks can result in heart failure due to ongoing inflammation and scarring. This research investigates how a specific protein, IKKε, affects inflammation in heart cells. Researchers used genetically altered mice and sophisticated genetic methods to study IKKε‘s role in heart disease. They analyzed heart tissue after inducing heart attacks in the mice, focusing on how cells involved in inflammation and scarring behave differently when the IKKε protein is changed. Macrophage-myofibroblast transition (MMT) is a process in which macrophages acquire characteristics similar to myofibroblasts, potentially contributing to tissue fibrosis. The main discovery is that blocking IKKε causes more scarring by encouraging excessive MMT, suggesting it could be a target for heart disease treatment. The researchers believe that controlling the MMT process could be a new method to enhance heart health after a heart attack by reducing harmful scarring. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
NF-kB激酶ε抑制剂（IKKε）在心肌梗死（MI）后炎症中的调节作用仍不确定。我们利用心肌梗死小鼠模型，研究了IKKε基因敲除（KO）小鼠和野生型小鼠的心脏预后。我们采用了单细胞 RNA 测序（scRNA-seq）和磷酸化蛋白阵列技术来分析心脏巨噬细胞。IKKε KO小鼠表现出存活率下降、炎症加剧、明显的心脏纤维化和射血分数降低。IKKε KO 小鼠中一个独特的心脏巨噬细胞亚群表现出纤维化标志物表达增加和磷酸化 p38（p-p38）水平降低，表明心肌梗死后巨噬细胞-肌成纤维细胞转化（MMT）增强。虽然心脏炎症是启动代偿途径的关键，但在 IKKε KO 组中，炎症的及时解决受到了影响，而巨噬细胞的 MMT 在心肌梗死后加速，从而导致心力衰竭。此外，我们的研究还强调了 5-氮杂胞苷（5-Aza）在恢复受刺激巨噬细胞中 p-p38 水平方面的潜力，5-氮杂胞苷具有抗炎和保护心脏的作用。给予 5-Aza 能明显降低 IKKε KO 组心脏巨噬细胞中的 MMT。这些发现强调了IKKε-p38轴对炎症反应和巨噬细胞转化的调控作用，表明MMT是治疗缺血性心脏病的一个很有前景的靶点。
{"title":"IKKε-deficient macrophages impede cardiac repair after myocardial infarction by enhancing the macrophage–myofibroblast transition","authors":"Hyang Hee Cho, Siyeon Rhee, Dong Im Cho, Ju Hee Jun, HyoJung Heo, Su Han Cho, Dohyup Kim, Mingqiang Wang, Bo Gyeong Kang, Soo Ji Yoo, Meeyoung Cho, Soo yeon Lim, Jae Yeong Cho, In Seok Jeong, Yong Sook Kim, Youngkeun Ahn","doi":"10.1038/s12276-024-01304-0","DOIUrl":"10.1038/s12276-024-01304-0","url":null,"abstract":"The regulatory role of the inhibitor of NF-kB kinase ε (IKKε) in postmyocardial infarction (MI) inflammation remains uncertain. Using an MI mouse model, we examined the cardiac outcomes of IKKε knockout (KO) mice and wild-type mice. We employed single-cell RNA sequencing (scRNA-seq) and phosphorylated protein array techniques to profile cardiac macrophages. IKKε KO mice exhibited compromised survival, heightened inflammation, pronounced cardiac fibrosis, and a reduced ejection fraction. A distinct cardiac macrophage subset in IKKε KO mice exhibited increased fibrotic marker expression and decreased phosphorylated p38 (p-p38) levels, indicating an enhanced macrophage–myofibroblast transition (MMT) post-MI. While cardiac inflammation is crucial for initiating compensatory pathways, the timely resolution of inflammation was impaired in the IKKε KO group, while the MMT in macrophages accelerated post-MI, leading to cardiac failure. Additionally, our study highlighted the potential of 5-azacytidine (5-Aza), known for its anti-inflammatory and cardioprotective effects, in restoring p-p38 levels in stimulated macrophages. The administration of 5-Aza significantly reduced the MMT in cardiac macrophages from the IKKε KO group. These findings underscore the regulation of the inflammatory response and macrophage transition by the IKKε-p38 axis, indicating that the MMT is a promising therapeutic target for ischemic heart disease. Heart attacks can result in heart failure due to ongoing inflammation and scarring. This research investigates how a specific protein, IKKε, affects inflammation in heart cells. Researchers used genetically altered mice and sophisticated genetic methods to study IKKε‘s role in heart disease. They analyzed heart tissue after inducing heart attacks in the mice, focusing on how cells involved in inflammation and scarring behave differently when the IKKε protein is changed. Macrophage-myofibroblast transition (MMT) is a process in which macrophages acquire characteristics similar to myofibroblasts, potentially contributing to tissue fibrosis. The main discovery is that blocking IKKε causes more scarring by encouraging excessive MMT, suggesting it could be a target for heart disease treatment. The researchers believe that controlling the MMT process could be a new method to enhance heart health after a heart attack by reducing harmful scarring. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01304-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-04DOI: 10.1038/s12276-024-01305-z
Gi Uk Jeong, Insu Hwang, Wooseong Lee, Ji Hyun Choi, Gun Young Yoon, Hae Soo Kim, Jeong-Sun Yang, Kyung-Chang Kim, Joo-Yeon Lee, Seong-Jun Kim, Young-Chan Kwon, Kyun-Do Kim
{"title":"Author Correction: Generation of a lethal mouse model expressing human ACE2 and TMPRSS2 for SARS-CoV-2 infection and pathogenesis","authors":"Gi Uk Jeong, Insu Hwang, Wooseong Lee, Ji Hyun Choi, Gun Young Yoon, Hae Soo Kim, Jeong-Sun Yang, Kyung-Chang Kim, Joo-Yeon Lee, Seong-Jun Kim, Young-Chan Kwon, Kyun-Do Kim","doi":"10.1038/s12276-024-01305-z","DOIUrl":"10.1038/s12276-024-01305-z","url":null,"abstract":"","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01305-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-04DOI: 10.1038/s12276-024-01310-2
Cristiano Fieni, Carlo Sorrentino, Stefania Livia Ciummo, Antonella Fontana, Lavinia Vittoria Lotti, Sofia Scialis, Darien Calvo Garcia, Massimo Caulo, Emma Di Carlo
The development of selective and nontoxic immunotherapy targeting prostate cancer (PC) is challenging. Interleukin (IL)30 plays immunoinhibitory and oncogenic roles in PC, and its tumor-specific suppression may have significant clinical implications. CRISPR/Cas9-mediated IL30 gene deletion in PC xenografts using anti-PSCA antibody-driven lipid nanocomplexes (Cas9gRNA-hIL30-PSCA NxPs) revealed significant genome editing efficiency and circulation stability without off-target effects or organ toxicity. Biweekly intravenous administration of Cas9gRNA-hIL30-PSCA NxPs to PC-bearing mice inhibited tumor growth and metastasis and improved survival. Mechanistically, Cas9gRNA-hIL30-PSCA NxPs suppressed ANGPTL 1/2/4, IL1β, CCL2, CXCL1/6, SERPINE1-F1, EFNB2, PLG, PF4, VEGFA, VEGFD, ANG, TGFβ1, EGF and HGF expression in human PC cells while upregulated CDH1, DKK3 and PTEN expression, leading to low proliferation and extensive ischemic necrosis. In the syngeneic PC model, IL30-targeting immunoliposomes downregulated NFKB1 expression and prevented intratumoral influx of CD11b+Gr-1+MDCs, Foxp3+Tregs, and NKp46+RORγt+ILC3, and prolonged host survival by inhibiting tumor progression. This study serves as a proof of principle that immunoliposome-based targeted delivery of Cas9gRNA-IL30 represent a potentially safe and effective strategy for PC treatment. Prostate cancer is an age-related disease and a leading cause of cancer death in men worldwide. Although its incidence has remained stable over the past decade, the proportion of tumors diagnosed in the advanced stages is rising, highlighting the need for improved and personalized treatments, especially for older patients with additional health problems. Di Carlo and coworkers created a NanoLiposome delivery system to transport a gene-editing tool, CRISPR/Cas9, directly to prostate cancer cells, to target and inhibit a particular gene involved in cancer growth. This study tested this approach’s effectiveness and safety on human prostate cancer cells and mouse models. The findings show the potential of using NanoLiposomes for targeted gene editing in cancer. The researchers conclude that this method could provide a new and effective way to treat prostate cancer, particularly in patients requiring gentler treatment options. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"Immunoliposome-based targeted delivery of the CRISPR/Cas9gRNA-IL30 complex inhibits prostate cancer and prolongs survival","authors":"Cristiano Fieni, Carlo Sorrentino, Stefania Livia Ciummo, Antonella Fontana, Lavinia Vittoria Lotti, Sofia Scialis, Darien Calvo Garcia, Massimo Caulo, Emma Di Carlo","doi":"10.1038/s12276-024-01310-2","DOIUrl":"10.1038/s12276-024-01310-2","url":null,"abstract":"The development of selective and nontoxic immunotherapy targeting prostate cancer (PC) is challenging. Interleukin (IL)30 plays immunoinhibitory and oncogenic roles in PC, and its tumor-specific suppression may have significant clinical implications. CRISPR/Cas9-mediated IL30 gene deletion in PC xenografts using anti-PSCA antibody-driven lipid nanocomplexes (Cas9gRNA-hIL30-PSCA NxPs) revealed significant genome editing efficiency and circulation stability without off-target effects or organ toxicity. Biweekly intravenous administration of Cas9gRNA-hIL30-PSCA NxPs to PC-bearing mice inhibited tumor growth and metastasis and improved survival. Mechanistically, Cas9gRNA-hIL30-PSCA NxPs suppressed ANGPTL 1/2/4, IL1β, CCL2, CXCL1/6, SERPINE1-F1, EFNB2, PLG, PF4, VEGFA, VEGFD, ANG, TGFβ1, EGF and HGF expression in human PC cells while upregulated CDH1, DKK3 and PTEN expression, leading to low proliferation and extensive ischemic necrosis. In the syngeneic PC model, IL30-targeting immunoliposomes downregulated NFKB1 expression and prevented intratumoral influx of CD11b+Gr-1+MDCs, Foxp3+Tregs, and NKp46+RORγt+ILC3, and prolonged host survival by inhibiting tumor progression. This study serves as a proof of principle that immunoliposome-based targeted delivery of Cas9gRNA-IL30 represent a potentially safe and effective strategy for PC treatment. Prostate cancer is an age-related disease and a leading cause of cancer death in men worldwide. Although its incidence has remained stable over the past decade, the proportion of tumors diagnosed in the advanced stages is rising, highlighting the need for improved and personalized treatments, especially for older patients with additional health problems. Di Carlo and coworkers created a NanoLiposome delivery system to transport a gene-editing tool, CRISPR/Cas9, directly to prostate cancer cells, to target and inhibit a particular gene involved in cancer growth. This study tested this approach’s effectiveness and safety on human prostate cancer cells and mouse models. The findings show the potential of using NanoLiposomes for targeted gene editing in cancer. The researchers conclude that this method could provide a new and effective way to treat prostate cancer, particularly in patients requiring gentler treatment options. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01310-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1038/s12276-024-01294-z
Sang Ho Yoon, Woo Seok Song, Geehoon Chung, Sang Jeong Kim, Myoung-Hwan Kim
Anatomical connectivity and lesion-deficit studies have shown that the dorsal and ventral hippocampi contribute to cognitive and emotional processes, respectively. However, the role of the dorsal hippocampus (dHP) in emotional or stress-related behaviors remains unclear. Here, we showed that neuronal activity in the dHP affects stress-coping behaviors in mice via excitatory projections to the medial prefrontal cortex (mPFC). The antidepressant ketamine rapidly induced c-Fos expression in both the dorsal and ventral hippocampi. The suppression of GABAergic transmission in the dHP-induced molecular changes similar to those induced by ketamine administration, including eukaryotic elongation factor 2 (eEF2) dephosphorylation, brain-derived neurotrophic factor (BDNF) elevation, and extracellular signal-regulated kinase (ERK) phosphorylation. These synaptic and molecular changes in the dHP induced a reduction in the immobility time of the mice in the tail-suspension and forced swim tests without affecting anxiety-related behavior. Conversely, pharmacological and chemogenetic potentiation of inhibitory neurotransmission in the dHP CA1 region induced passive coping behaviors during the tests. Transneuronal tracing and electrophysiology revealed monosynaptic excitatory connections between dHP CA1 neurons and mPFC neurons. Optogenetic stimulation of dHP CA1 neurons in freely behaving mice produced c-Fos induction and spike firing in the mPFC neurons. Chemogenetic activation of the dHP-recipient mPFC neurons reversed the passive coping behaviors induced by suppression of dHP CA1 neuronal activity. Collectively, these results indicate that neuronal activity in the dHP modulates stress-coping strategies to inescapable stress and contributes to the antidepressant effects of ketamine via the dHP-mPFC circuit. Understanding our brain’s handling of emotions and thought is vital. Recent research indicates that different sections of the hippocampus are responsible for either thought processing or emotional reactions. However, new research by Yoon et al. disputes this, demonstrating that both hippocampus sections can affect behavior via connections with the prefrontal cortex, a brain area involved in decision-making. This study, a mouse experiment, examined how a specific pathway between the dorsal hippocampus and the medial prefrontal cortex impacts behavior, especially in response to stress and depression-like symptoms. The researchers used various methods, including gene alteration and behavioral tests, to understand how changes in this pathway’s activity affect behavior. This study paves the way for future research to explore how these brain areas interact in the context of emotional and thought processing, potentially leading to more effective depression treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"Activity in the dorsal hippocampus-mPFC circuit modulates stress-coping strategies during inescapable stress","authors":"Sang Ho Yoon, Woo Seok Song, Geehoon Chung, Sang Jeong Kim, Myoung-Hwan Kim","doi":"10.1038/s12276-024-01294-z","DOIUrl":"10.1038/s12276-024-01294-z","url":null,"abstract":"Anatomical connectivity and lesion-deficit studies have shown that the dorsal and ventral hippocampi contribute to cognitive and emotional processes, respectively. However, the role of the dorsal hippocampus (dHP) in emotional or stress-related behaviors remains unclear. Here, we showed that neuronal activity in the dHP affects stress-coping behaviors in mice via excitatory projections to the medial prefrontal cortex (mPFC). The antidepressant ketamine rapidly induced c-Fos expression in both the dorsal and ventral hippocampi. The suppression of GABAergic transmission in the dHP-induced molecular changes similar to those induced by ketamine administration, including eukaryotic elongation factor 2 (eEF2) dephosphorylation, brain-derived neurotrophic factor (BDNF) elevation, and extracellular signal-regulated kinase (ERK) phosphorylation. These synaptic and molecular changes in the dHP induced a reduction in the immobility time of the mice in the tail-suspension and forced swim tests without affecting anxiety-related behavior. Conversely, pharmacological and chemogenetic potentiation of inhibitory neurotransmission in the dHP CA1 region induced passive coping behaviors during the tests. Transneuronal tracing and electrophysiology revealed monosynaptic excitatory connections between dHP CA1 neurons and mPFC neurons. Optogenetic stimulation of dHP CA1 neurons in freely behaving mice produced c-Fos induction and spike firing in the mPFC neurons. Chemogenetic activation of the dHP-recipient mPFC neurons reversed the passive coping behaviors induced by suppression of dHP CA1 neuronal activity. Collectively, these results indicate that neuronal activity in the dHP modulates stress-coping strategies to inescapable stress and contributes to the antidepressant effects of ketamine via the dHP-mPFC circuit. Understanding our brain’s handling of emotions and thought is vital. Recent research indicates that different sections of the hippocampus are responsible for either thought processing or emotional reactions. However, new research by Yoon et al. disputes this, demonstrating that both hippocampus sections can affect behavior via connections with the prefrontal cortex, a brain area involved in decision-making. This study, a mouse experiment, examined how a specific pathway between the dorsal hippocampus and the medial prefrontal cortex impacts behavior, especially in response to stress and depression-like symptoms. The researchers used various methods, including gene alteration and behavioral tests, to understand how changes in this pathway’s activity affect behavior. This study paves the way for future research to explore how these brain areas interact in the context of emotional and thought processing, potentially leading to more effective depression treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01294-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1038/s12276-024-01298-9
Ling Luo, Fupeng Wang, Xueming Xu, Mingliang Ma, Guangyan Kuang, Yening Zhang, Dan Wang, Wei Li, Ningjie Zhang, Kai Zhao
Recognition of the translocation of NLRP3 to various organelles has provided new insights for understanding how the NLRP3 inflammasome is activated by different stimuli. Mitochondria have already been demonstrated to be the site of NLRP3 inflammasome activation, and the latest research suggests that NLRP3 is first recruited to mitochondria, then disassociated, and subsequently recruited to the Golgi network. Although some mitochondrial factors have been found to contribute to the recruitment of NLRP3 to mitochondria, the detailed process of NLRP3 mitochondrial translocation remains unclear. Here, we identify a previously unknown role for Signal transducer and activator of transcription-3 (STAT3) in facilitating the translocation of NLRP3 to mitochondria. STAT3 interacts with NLRP3 and undergoes phosphorylation at Ser727 in response to several NLRP3 agonists, enabling the translocation of STAT3 and thus the bound NLRP3 to mitochondria. Disruption of the interaction between STAT3 and NLRP3 impairs the mitochondrial localization of NLRP3, specifically suppressing NLRP3 inflammasome activation both in vitro and in vivo. In summary, we demonstrate that STAT3 acts as a transporter for mitochondrial translocation of NLRP3 and provide new insight into the spatial regulation of NLRP3. Our bodies have an innate immune system, which is the first line of defense against infections. It uses specific receptors to detect harmful pathogens. This research investigates how a protein, STAT3, affects the activation of a complex, the NLRP3 inflammasome, crucial in our immune response. The study involved experiments with cell cultures and mice, identifying how STAT3 helps move NLRP3 within cells for activation. This was seen in an experimental study. The results show that targeting STAT3 can reduce inflammation caused by the NLRP3 inflammasome. This suggests a new treatment strategy for diseases caused by too much inflammation, like gout, diabetes, and Alzheimer’s disease. The study shows the potential of drugs that stop STAT3 to manage or treat inflammatory conditions, paving the way for future research on such treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"STAT3 promotes NLRP3 inflammasome activation by mediating NLRP3 mitochondrial translocation","authors":"Ling Luo, Fupeng Wang, Xueming Xu, Mingliang Ma, Guangyan Kuang, Yening Zhang, Dan Wang, Wei Li, Ningjie Zhang, Kai Zhao","doi":"10.1038/s12276-024-01298-9","DOIUrl":"10.1038/s12276-024-01298-9","url":null,"abstract":"Recognition of the translocation of NLRP3 to various organelles has provided new insights for understanding how the NLRP3 inflammasome is activated by different stimuli. Mitochondria have already been demonstrated to be the site of NLRP3 inflammasome activation, and the latest research suggests that NLRP3 is first recruited to mitochondria, then disassociated, and subsequently recruited to the Golgi network. Although some mitochondrial factors have been found to contribute to the recruitment of NLRP3 to mitochondria, the detailed process of NLRP3 mitochondrial translocation remains unclear. Here, we identify a previously unknown role for Signal transducer and activator of transcription-3 (STAT3) in facilitating the translocation of NLRP3 to mitochondria. STAT3 interacts with NLRP3 and undergoes phosphorylation at Ser727 in response to several NLRP3 agonists, enabling the translocation of STAT3 and thus the bound NLRP3 to mitochondria. Disruption of the interaction between STAT3 and NLRP3 impairs the mitochondrial localization of NLRP3, specifically suppressing NLRP3 inflammasome activation both in vitro and in vivo. In summary, we demonstrate that STAT3 acts as a transporter for mitochondrial translocation of NLRP3 and provide new insight into the spatial regulation of NLRP3. Our bodies have an innate immune system, which is the first line of defense against infections. It uses specific receptors to detect harmful pathogens. This research investigates how a protein, STAT3, affects the activation of a complex, the NLRP3 inflammasome, crucial in our immune response. The study involved experiments with cell cultures and mice, identifying how STAT3 helps move NLRP3 within cells for activation. This was seen in an experimental study. The results show that targeting STAT3 can reduce inflammation caused by the NLRP3 inflammasome. This suggests a new treatment strategy for diseases caused by too much inflammation, like gout, diabetes, and Alzheimer’s disease. The study shows the potential of drugs that stop STAT3 to manage or treat inflammatory conditions, paving the way for future research on such treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01298-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1038/s12276-024-01295-y
Sunwoo Chung, June-Hyun Jeong, Jong-Chan Park, Jong Won Han, Yeajina Lee, Jong-Il Kim, Inhee Mook-Jung
Abnormal glial activation promotes neurodegeneration in Alzheimer’s disease (AD), the most common cause of dementia. Stimulation of the cGAS-STING pathway induces microglial dysfunction and sterile inflammation, which exacerbates AD. We showed that inhibiting STING activation can control microglia and ameliorate a wide spectrum of AD symptoms. The cGAS-STING pathway is required for the detection of ectopic DNA and the subsequent immune response. Amyloid-β (Aβ) and tau induce mitochondrial stress, which causes DNA to be released into the cytoplasm of microglia. cGAS and STING are highly expressed in Aβ plaque-associated microglia, and neuronal STING is upregulated in the brains of AD model animals. The presence of the APOE ε4 allele, an AD risk factor, also upregulated both proteins. STING activation was necessary for microglial NLRP3 activation, proinflammatory responses, and type-I-interferon responses. Pharmacological STING inhibition reduced a wide range of AD pathogenic features in AppNL-G-F/hTau double-knock-in mice. An unanticipated transcriptome shift in microglia reduced gliosis and cerebral inflammation. Significant reductions in the Aβ load, tau phosphorylation, and microglial synapse engulfment prevented memory loss. To summarize, our study describes the pathogenic mechanism of STING activation as well as its potential as a therapeutic target in AD. In illnesses like Alzheimer’s that cause brain deterioration, the brain’s defense cells, known as microglia, overreact due to harmful proteins, causing brain damage and memory loss. This research aimed to understand how microglia change in Alzheimer’s and find ways to stop their damaging effects. Using mice with Alzheimer’s, they checked if blocking specific immune pathway could fix microglia dysfunction and Alzheimer’s disease pathologies. They discovered that blocking STING, a crucial part of this pathway, reduced microglia dysfunction brain inflammation, decreased the buildup of Alzheimer’s-related proteins, and improved memory in mice. By blocking the STING activation, the study showed a decrease in damaging brain inflammation and improvements in memory function, suggesting a promising strategy for treating Alzheimer’s. Researchers conclude that targeting the STING could offer a new way to fight Alzheimer’s by reducing inflammation and protecting brain health. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
神经胶质的异常激活会促进阿尔茨海默病（AD）的神经变性，而阿尔茨海默病是导致痴呆症的最常见原因。cGAS-STING 通路的刺激会诱发小胶质细胞功能障碍和无菌性炎症，从而加剧阿尔茨海默病。我们的研究表明，抑制 STING 的激活可以控制小胶质细胞，并改善多种 AD 症状。cGAS-STING 通路是检测异位 DNA 和随后的免疫反应所必需的。淀粉样蛋白-β（Aβ）和tau诱导线粒体应激，导致DNA释放到小胶质细胞的胞浆中。作为AD风险因子的APOE ε4等位基因的存在也会上调这两种蛋白。STING 激活是小胶质细胞 NLRP3 激活、促炎反应和 I 型干扰素反应的必要条件。药理 STING 抑制可减少 AppNL-G-F/hTau 双基因敲入小鼠的多种 AD 致病特征。小胶质细胞的转录组发生了意想不到的变化，从而减少了胶质细胞增生和脑部炎症。Aβ负荷、tau磷酸化和小胶质细胞突触吞噬的显著减少防止了记忆丧失。总之，我们的研究描述了 STING 激活的致病机制及其作为 AD 治疗靶点的潜力。
{"title":"Blockade of STING activation alleviates microglial dysfunction and a broad spectrum of Alzheimer’s disease pathologies","authors":"Sunwoo Chung, June-Hyun Jeong, Jong-Chan Park, Jong Won Han, Yeajina Lee, Jong-Il Kim, Inhee Mook-Jung","doi":"10.1038/s12276-024-01295-y","DOIUrl":"10.1038/s12276-024-01295-y","url":null,"abstract":"Abnormal glial activation promotes neurodegeneration in Alzheimer’s disease (AD), the most common cause of dementia. Stimulation of the cGAS-STING pathway induces microglial dysfunction and sterile inflammation, which exacerbates AD. We showed that inhibiting STING activation can control microglia and ameliorate a wide spectrum of AD symptoms. The cGAS-STING pathway is required for the detection of ectopic DNA and the subsequent immune response. Amyloid-β (Aβ) and tau induce mitochondrial stress, which causes DNA to be released into the cytoplasm of microglia. cGAS and STING are highly expressed in Aβ plaque-associated microglia, and neuronal STING is upregulated in the brains of AD model animals. The presence of the APOE ε4 allele, an AD risk factor, also upregulated both proteins. STING activation was necessary for microglial NLRP3 activation, proinflammatory responses, and type-I-interferon responses. Pharmacological STING inhibition reduced a wide range of AD pathogenic features in AppNL-G-F/hTau double-knock-in mice. An unanticipated transcriptome shift in microglia reduced gliosis and cerebral inflammation. Significant reductions in the Aβ load, tau phosphorylation, and microglial synapse engulfment prevented memory loss. To summarize, our study describes the pathogenic mechanism of STING activation as well as its potential as a therapeutic target in AD. In illnesses like Alzheimer’s that cause brain deterioration, the brain’s defense cells, known as microglia, overreact due to harmful proteins, causing brain damage and memory loss. This research aimed to understand how microglia change in Alzheimer’s and find ways to stop their damaging effects. Using mice with Alzheimer’s, they checked if blocking specific immune pathway could fix microglia dysfunction and Alzheimer’s disease pathologies. They discovered that blocking STING, a crucial part of this pathway, reduced microglia dysfunction brain inflammation, decreased the buildup of Alzheimer’s-related proteins, and improved memory in mice. By blocking the STING activation, the study showed a decrease in damaging brain inflammation and improvements in memory function, suggesting a promising strategy for treating Alzheimer’s. Researchers conclude that targeting the STING could offer a new way to fight Alzheimer’s by reducing inflammation and protecting brain health. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01295-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1038/s12276-024-01307-x
Sang Yean Kim, Min Jeong Na, Sungpil Yoon, Eunbi Shin, Jin Woong Ha, Soyoung Jeon, Suk Woo Nam
Functional variations in coding and noncoding RNAs are crucial in tumorigenesis, with cancer-specific alterations often resulting from chemical modifications and posttranscriptional processes mediated by enzymes. These RNA variations have been linked to tumor cell proliferation, growth, metastasis, and drug resistance and are valuable for identifying diagnostic or prognostic cancer biomarkers. The diversity of posttranscriptional RNA modifications, such as splicing, polyadenylation, methylation, and editing, is particularly significant due to their prevalence and impact on cancer progression. Additionally, other modifications, including RNA acetylation, circularization, miRNA isomerization, and pseudouridination, are recognized as key contributors to cancer development. Understanding the mechanisms underlying these RNA modifications in cancer can enhance our knowledge of cancer biology and facilitate the development of innovative therapeutic strategies. Targeting these RNA modifications and their regulatory enzymes may pave the way for novel RNA-based therapies, enabling tailored interventions for specific cancer subtypes. This review provides a comprehensive overview of the roles and mechanisms of various coding and noncoding RNA modifications in cancer progression and highlights recent advancements in RNA-based therapeutic applications. In the intricate field of cancer study, researchers investigate how changes in RNA, a molecule that carries genetic instructions, contribute to cancer. Researchers explores these RNA changes, their mechanisms, and their role in cancer development. The authors review various ways RNA can be modified, including methylation, editing, and alternative splicing. The authors underline how these RNA changes can impact cancer development by affecting gene activity, protein creation, and cell behavior. The review’s key findings suggest that RNA changes are deeply involved in cancer’s start, development, and treatment response. By charting the landscape of RNA changes in cancer cells, the authors aim to pave new paths for diagnosis, prognosis, and treatment. They conclude targeting RNA changes offers a promising strategy for developing innovative cancer treatments, marking a significant progress in our approach to fighting this disease. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"The roles and mechanisms of coding and noncoding RNA variations in cancer","authors":"Sang Yean Kim, Min Jeong Na, Sungpil Yoon, Eunbi Shin, Jin Woong Ha, Soyoung Jeon, Suk Woo Nam","doi":"10.1038/s12276-024-01307-x","DOIUrl":"10.1038/s12276-024-01307-x","url":null,"abstract":"Functional variations in coding and noncoding RNAs are crucial in tumorigenesis, with cancer-specific alterations often resulting from chemical modifications and posttranscriptional processes mediated by enzymes. These RNA variations have been linked to tumor cell proliferation, growth, metastasis, and drug resistance and are valuable for identifying diagnostic or prognostic cancer biomarkers. The diversity of posttranscriptional RNA modifications, such as splicing, polyadenylation, methylation, and editing, is particularly significant due to their prevalence and impact on cancer progression. Additionally, other modifications, including RNA acetylation, circularization, miRNA isomerization, and pseudouridination, are recognized as key contributors to cancer development. Understanding the mechanisms underlying these RNA modifications in cancer can enhance our knowledge of cancer biology and facilitate the development of innovative therapeutic strategies. Targeting these RNA modifications and their regulatory enzymes may pave the way for novel RNA-based therapies, enabling tailored interventions for specific cancer subtypes. This review provides a comprehensive overview of the roles and mechanisms of various coding and noncoding RNA modifications in cancer progression and highlights recent advancements in RNA-based therapeutic applications. In the intricate field of cancer study, researchers investigate how changes in RNA, a molecule that carries genetic instructions, contribute to cancer. Researchers explores these RNA changes, their mechanisms, and their role in cancer development. The authors review various ways RNA can be modified, including methylation, editing, and alternative splicing. The authors underline how these RNA changes can impact cancer development by affecting gene activity, protein creation, and cell behavior. The review’s key findings suggest that RNA changes are deeply involved in cancer’s start, development, and treatment response. By charting the landscape of RNA changes in cancer cells, the authors aim to pave new paths for diagnosis, prognosis, and treatment. They conclude targeting RNA changes offers a promising strategy for developing innovative cancer treatments, marking a significant progress in our approach to fighting this disease. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01307-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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