Pub Date : 2024-04-01DOI: 10.1615/critreveukaryotgeneexpr.2024053036
Yasaman Daneshian, Eric Lewallen, Amr Badreldin, Allan Dietz, Gary Stein, Simon Cool, Hyun-Mo Ryoo, Young Dan Cho, Andre van Wijnen
Regenerative dental medicine continuously expands to improve treatments for prevalent clinical problems in dental and oral medicine. Stem cell based translational opportunities include regenerative therapies for tooth restoration, root canal therapy and inflammatory processes (e.g., periodontitis). The potential of regenerative approaches relies on the biological properties of dental stem cells. These and other multipotent somatic mesenchymal stem cell (MSC) types can in principle be applied as either autologous or allogeneic sources in dental procedures. Dental stem cells have distinct developmental origins and biological markers that determine their translational utility. Dental regenerative medicine is supported by mechanistic knowledge of the molecular pathways that regulate dental stem cell growth and differentiation. Cell fate determination and lineage progression of dental stem cells is regulated by multiple cell signaling pathways (e.g., WNTs, BMPs) and epigenetic mechanisms, including DNA modifications, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs). This review also considers a broad range of novel approaches in which stem cells are applied in combination with biopolymers, ceramics and composite materials, as well as small molecules (agonistic or anti-agonistic ligands) and natural compounds. Promising concepts in bone and dental tissue engineering continue to drive innovation in dental and non-dental restorative procedures.
{"title":"Fundamentals and translational applications of stem cells and biomaterials in dental, oral and craniofacial regenerative medicine","authors":"Yasaman Daneshian, Eric Lewallen, Amr Badreldin, Allan Dietz, Gary Stein, Simon Cool, Hyun-Mo Ryoo, Young Dan Cho, Andre van Wijnen","doi":"10.1615/critreveukaryotgeneexpr.2024053036","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024053036","url":null,"abstract":"Regenerative dental medicine continuously expands to improve treatments for prevalent clinical problems in dental and oral medicine. Stem cell based translational opportunities include regenerative therapies for tooth restoration, root canal therapy and inflammatory processes (e.g., periodontitis). The potential of regenerative approaches relies on the biological properties of dental stem cells. These and other multipotent somatic mesenchymal stem cell (MSC) types can in principle be applied as either autologous or allogeneic sources in dental procedures. Dental stem cells have distinct developmental origins and biological markers that determine their translational utility. Dental regenerative medicine is supported by mechanistic knowledge of the molecular pathways that regulate dental stem cell growth and differentiation. Cell fate determination and lineage progression of dental stem cells is regulated by multiple cell signaling pathways (e.g., WNTs, BMPs) and epigenetic mechanisms, including DNA modifications, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs). This review also considers a broad range of novel approaches in which stem cells are applied in combination with biopolymers, ceramics and composite materials, as well as small molecules (agonistic or anti-agonistic ligands) and natural compounds. Promising concepts in bone and dental tissue engineering continue to drive innovation in dental and non-dental restorative procedures.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"188 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1615/critreveukaryotgeneexpr.2024052889
William Cates, Janet Denbeigh, Ralph Salvagno, Sanjeev Kakar, Andre van Wijnen, Charles Eaton
Dupuytren Disease is a common fibroproliferative disease that can result in debilitating hand deformities. Partial correction and return of deformity are common with surgical or clinical treatments at present. While current treatments are limited to local procedures for relatively late effects of the disease, the pathophysiology of this connective tissue disorder is associated with both local and systemic processes (e.g., fibrosis, inflammation). Hence, a better understanding of the systemic circulation of Dupuytren related cytokines and growth factors may provide important insights into disease progression. In addition, systemic biomarker analysis could yield new concepts for treatments of Dupuytren that attenuate circulatory factors (e.g., anti-inflammatory agents, neutralizing antibodies). Progress in the development of any disease modifying biologic treatment for Dupuytren has been hampered by the lack of clinically useful biomarkers. The characterization of nonsurgical Dupuytren biomarkers will permit disease staging from diagnostic and prognostic perspectives, as well as allows evaluation of biologic responses to treatment. Identification of such markers may transcend their use in Dupuytren treatment, because fibrotic biological processes fundamental to Dupuytren are relevant to fibrosis in many other connective tissues and organs with collagen-based tissue compartments. There is a wide range of potential Dupuytren biomarker categories that could be informative, including disease determinants linked to genetics, collagen metabolism, as well as immunity and inflammation (e.g., cytokines, chemokines). This narrative review provides a broad overview of previous studies
{"title":"Inflammatory Markers Involved in the Pathogenesis of Dupuytren Contracture","authors":"William Cates, Janet Denbeigh, Ralph Salvagno, Sanjeev Kakar, Andre van Wijnen, Charles Eaton","doi":"10.1615/critreveukaryotgeneexpr.2024052889","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024052889","url":null,"abstract":"Dupuytren Disease is a common fibroproliferative disease that can result in debilitating hand deformities. Partial correction and return of deformity are common with surgical or clinical treatments at present. While current treatments are limited to local procedures for relatively late effects of the disease, the pathophysiology of this connective tissue disorder is associated with both local and systemic processes (e.g., fibrosis, inflammation). Hence, a better understanding of the systemic circulation of Dupuytren related cytokines and growth factors may provide important insights into disease progression. In addition, systemic biomarker analysis could yield new concepts for treatments of Dupuytren that attenuate circulatory factors (e.g., anti-inflammatory agents, neutralizing antibodies). Progress in the development of any disease modifying biologic treatment for Dupuytren has been hampered by the lack of clinically useful biomarkers. The characterization of nonsurgical Dupuytren biomarkers will permit disease staging from diagnostic and prognostic perspectives, as well as allows evaluation of biologic responses to treatment. Identification of such markers may transcend their use in Dupuytren treatment, because fibrotic biological processes fundamental to Dupuytren are relevant to fibrosis in many other connective tissues and organs with collagen-based tissue compartments. There is a wide range of potential Dupuytren biomarker categories that could be informative, including disease determinants linked to genetics, collagen metabolism, as well as immunity and inflammation (e.g., cytokines, chemokines). This narrative review provides a broad overview of previous studies","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"313 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1615/critreveukaryotgeneexpr.2024053672
Scott Perrapato, Nicholas Farina, Adrian Berg, James Wallace, Steven Ades, Thomas Ahern, Janet Stein, Gary Stein, Jane Lian
Objective criteria are required for prostate cancer risk assessment, treatment decisions, evaluation of therapy, and initial indications of recurrence. Circulating microRNAs were utilized as biomarkers to distinguish prostate cancer patients from cancer-free subjects or those encountering benign prostate hyperplasia. A panel of sixty microRNAs was developed with established roles in prostate cancer initiation, progression, metastasis, and recurrence. Utilizing the FirePlex® platform for microRNA analysis, we demonstrated the efficacy and reproducibility of a rapid, high-throughput, serum-based assay for prostate cancer biomarkers that circumvents the requirement for extraction and fractionation of patient specimens supporting feasibility for expanded clinical research and diagnostic applications.
{"title":"A MicroRNA Approach to Evaluate Elevated Prostate Cancer Risk in Cancer-Free Men","authors":"Scott Perrapato, Nicholas Farina, Adrian Berg, James Wallace, Steven Ades, Thomas Ahern, Janet Stein, Gary Stein, Jane Lian","doi":"10.1615/critreveukaryotgeneexpr.2024053672","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024053672","url":null,"abstract":"Objective criteria are required for prostate cancer risk assessment, treatment decisions, evaluation of therapy, and initial indications of recurrence. Circulating microRNAs were utilized as biomarkers to distinguish prostate cancer patients from cancer-free subjects or those encountering benign prostate hyperplasia. A panel of sixty microRNAs was developed with established roles in prostate cancer initiation, progression, metastasis, and recurrence. Utilizing the FirePlex® platform for microRNA analysis, we demonstrated the efficacy and reproducibility of a rapid, high-throughput, serum-based assay for prostate cancer biomarkers that circumvents the requirement for extraction and fractionation of patient specimens supporting feasibility for expanded clinical research and diagnostic applications.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"40 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140811694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1615/critreveukaryotgeneexpr.2024052788
Jipeng Guo, Chongwen Gong, Hao Wang
Lung cancer is the most common malignancy worldwide. Long non-coding RNA (lncRNA) PURPL is abnormally in various cancers. However, the reports on its roles in lung cancer are limited. The purpose of present study is to investigate the potentials of lncRNA PURPL in lung cancer. PURPL and mRNA expression was determined using RT-qPCR. The location of PURPL was detected using RNA FISH assay. Protein expression was detected using western blot. Cellular functions were determined using flow cytometry. The interaction between PURPL and RBM4 was confirmed using RIP assay. PURPL was overexpressed in lung cancer cells and patients. Overexpressed PURPL promoted M2 macrophage polarization and suppressed ferroptosis. Additionally, PURPL maintained the mRNA stability of xCT via regulating RBM4. xCT knockdown antagonized the effects of overexpressed PURPL and inhibited M2 macrophage polarization via inducing macrophage ferroptosis. PURPL/RBM4/xCT axis promoted M2 macrophage polarization in lung cancer. Therefore, PURPL may be a potential target of lung cancer.
{"title":"PURPL promotes M2 macrophage polarization in lung cancer via regulating RBM4/xCT signaling","authors":"Jipeng Guo, Chongwen Gong, Hao Wang","doi":"10.1615/critreveukaryotgeneexpr.2024052788","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024052788","url":null,"abstract":"Lung cancer is the most common malignancy worldwide. Long non-coding RNA (lncRNA) PURPL is abnormally in various cancers. However, the reports on its roles in lung cancer are limited. The purpose of present study is to investigate the potentials of lncRNA PURPL in lung cancer. PURPL and mRNA expression was determined using RT-qPCR. The location of PURPL was detected using RNA FISH assay. Protein expression was detected using western blot. Cellular functions were determined using flow cytometry. The interaction between PURPL and RBM4 was confirmed using RIP assay. PURPL was overexpressed in lung cancer cells and patients. Overexpressed PURPL promoted M2 macrophage polarization and suppressed ferroptosis. Additionally, PURPL maintained the mRNA stability of xCT via regulating RBM4. xCT knockdown antagonized the effects of overexpressed PURPL and inhibited M2 macrophage polarization via inducing macrophage ferroptosis. PURPL/RBM4/xCT axis promoted M2 macrophage polarization in lung cancer. Therefore, PURPL may be a potential target of lung cancer.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"42 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140198193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1615/critreveukaryotgeneexpr.2024052979
Liang Xu, Fenger Zhang, Binqi Yu, Shengnan Jia, Sunfu Fan
Gastric cancer is a most malignancy in digestive tract worldwide. This study aimed to investigate the roles of PRMT6 in gastric cancer. Immunohistochemistry was performed to detect PRMT6 expression in gastric tumors. RT-qPCR was used to detected mRNA levels. Protein expression was determined using western blot. Gastric cancer cells were co-cultured with CD8+ T cells. Colony formation assay was performed to detect cell proliferation. Flow cytometry was performed to determine CD8+ T cell function and tumor cell apoptosis. PRMT6 was overexpressed in gastric tumors. High level of PRMT6 predicted poor outcomes of gastric cancer patients and inhibition of CD8+ T cell infiltration. PRMT6 promoted proliferation of CD8+ T cells and enhanced its tumor killing ability. Moreover, PRMT6 upregulated ANXA1 and promoted ANXA1 protein stability. ANXA1 overexpression suppressed the proliferation of CD8+ T cells and promoted tumor cell survival. PRMT6 functions as an oncogene in gastric cancer. PRMT6-mediated protein stability inhibits the infiltration of CD8+ T cells, resulting in immune evasion of gastric cancer. The PRMT6-ANXA1 may be a promising strategy for gastric cancer.
胃癌是全球消化道中最常见的恶性肿瘤。本研究旨在探讨 PRMT6 在胃癌中的作用。免疫组化法检测胃癌中 PRMT6 的表达。采用 RT-qPCR 检测 mRNA 水平。蛋白表达用 Western 印迹法测定。胃癌细胞与 CD8+ T 细胞共同培养。进行集落形成试验检测细胞增殖。流式细胞术检测 CD8+ T 细胞功能和肿瘤细胞凋亡。PRMT6在胃肿瘤中过表达。高水平的PRMT6预示着胃癌患者的不良预后以及对CD8+ T细胞浸润的抑制。PRMT6 促进了 CD8+ T 细胞的增殖，增强了其杀伤肿瘤的能力。此外，PRMT6 上调 ANXA1 并促进 ANXA1 蛋白的稳定性。ANXA1 的过表达抑制了 CD8+ T 细胞的增殖，促进了肿瘤细胞的存活。PRMT6是胃癌的致癌基因。PRMT6 介导的蛋白稳定性抑制了 CD8+ T 细胞的浸润，从而导致胃癌的免疫逃避。PRMT6-ANXA1可能是一种治疗胃癌的有前途的策略。
{"title":"PRMT6 promotes the immune evasion of gastric cancer via upregulating ANXA1","authors":"Liang Xu, Fenger Zhang, Binqi Yu, Shengnan Jia, Sunfu Fan","doi":"10.1615/critreveukaryotgeneexpr.2024052979","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024052979","url":null,"abstract":"Gastric cancer is a most malignancy in digestive tract worldwide. This study aimed to investigate the roles of PRMT6 in gastric cancer. Immunohistochemistry was performed to detect PRMT6 expression in gastric tumors. RT-qPCR was used to detected mRNA levels. Protein expression was determined using western blot. Gastric cancer cells were co-cultured with CD8+ T cells. Colony formation assay was performed to detect cell proliferation. Flow cytometry was performed to determine CD8+ T cell function and tumor cell apoptosis. PRMT6 was overexpressed in gastric tumors. High level of PRMT6 predicted poor outcomes of gastric cancer patients and inhibition of CD8+ T cell infiltration. PRMT6 promoted proliferation of CD8+ T cells and enhanced its tumor killing ability. Moreover, PRMT6 upregulated ANXA1 and promoted ANXA1 protein stability. ANXA1 overexpression suppressed the proliferation of CD8+ T cells and promoted tumor cell survival. PRMT6 functions as an oncogene in gastric cancer. PRMT6-mediated protein stability inhibits the infiltration of CD8+ T cells, resulting in immune evasion of gastric cancer. The PRMT6-ANXA1 may be a promising strategy for gastric cancer.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"29 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140316195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1615/critreveukaryotgeneexpr.2024052503
Yuanyuan Sun, Yaqing Li, Chengying Jiang, Chenying Liu, Yuanming Song
Breast cancer is one of the most common malignancy worldwide. SLC7A2 is abnormally expressed in multi-type cancers. However, the potentials of SLC7A2 in tripe negative breast cancer (TNBC) are still unclear. This study aimed to investigate the roles of SLC7A2 and the underlying molecular mechanisms. mRNA expression was detected by RT-qPCR. The release of cytokines was detected using ELISA. Protein expression was detected by western blot. Histone crotonylation was performed using in vitro histone crotonylation assay. functional analysis was performed using CCCK-8 and flow cytometry assay. Xenografting assay was conducted to further verify the roles of SLC7A2 in TNBC. The expression of CD8A was detected using immunohistochemistry. SLC7A2 was downregulated in TNBC tumors. Low levels of SLC7A2 were associated with advanced stages and lymph node metastasis. SLC7A2 expression was positive correlated with CD8A. SLC7A2-mediated lysine catabolism drove the activation of CD8+ T cells. Moreover, SLC7A2 promoted the histone crotonylationvia upregulating ACOX1 and downregulated CDYL. SLC7A2 promoted the interaction between ACOX1 and TCF1, resulting the proliferation of CD8+ T cells. Additionally, overexpression of SLC7A2 activated CD8+ T cells and enhanced the chemosensitivity of anti-PD-1 therapies in vivo. SLC7A2 may function as an anti-tumor gene in TNBC via activating anti-tumor immunity. Therefore, SLC7A2/ ACOX1/TCF1 signaling may be promising strategy for TNBC.
{"title":"SLC7A2-mediated lysine catabolism inhibits immunosuppression in triple negative breast cancer","authors":"Yuanyuan Sun, Yaqing Li, Chengying Jiang, Chenying Liu, Yuanming Song","doi":"10.1615/critreveukaryotgeneexpr.2024052503","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024052503","url":null,"abstract":"Breast cancer is one of the most common malignancy worldwide. SLC7A2 is abnormally expressed in multi-type cancers. However, the potentials of SLC7A2 in tripe negative breast cancer (TNBC) are still unclear. This study aimed to investigate the roles of SLC7A2 and the underlying molecular mechanisms. mRNA expression was detected by RT-qPCR. The release of cytokines was detected using ELISA. Protein expression was detected by western blot. Histone crotonylation was performed using in vitro histone crotonylation assay. functional analysis was performed using CCCK-8 and flow cytometry assay. Xenografting assay was conducted to further verify the roles of SLC7A2 in TNBC. The expression of CD8A was detected using immunohistochemistry. SLC7A2 was downregulated in TNBC tumors. Low levels of SLC7A2 were associated with advanced stages and lymph node metastasis. SLC7A2 expression was positive correlated with CD8A. SLC7A2-mediated lysine catabolism drove the activation of CD8+ T cells. Moreover, SLC7A2 promoted the histone crotonylationvia upregulating ACOX1 and downregulated CDYL. SLC7A2 promoted the interaction between ACOX1 and TCF1, resulting the proliferation of CD8+ T cells. Additionally, overexpression of SLC7A2 activated CD8+ T cells and enhanced the chemosensitivity of anti-PD-1 therapies in vivo. SLC7A2 may function as an anti-tumor gene in TNBC via activating anti-tumor immunity. Therefore, SLC7A2/ ACOX1/TCF1 signaling may be promising strategy for TNBC.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"11 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139764339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1615/critreveukaryotgeneexpr.2024052205
Ruixue Wang, Wenhua Tan
RBM15 functions as an oncogene in multi-type cancers. However, the report on the roles of RBM15 in cervical cancer is limited. The purpose of this study was to investigate the potentials of RBM15 in cervical cancer. RT-qPCR was conducted to determine mRNA levels. Western was carried out to detect protein expression. CCK-8 and colony formation assays were carried out to determine cell proliferation. Scratch and transwell assays were carried out to determine cell migration and invasion. MeRIP assay was conducted to determine N6-methyl adenosine (m6A) levels. Luciferase assay was conducted to verify the m6A sites of EZH2 and binding sites between cc and promoter of FN1. ChIP assay was conducted to verify the interaction between EZH2 and FN1. RBM15 was upregulated in cervical cancer tissues and cells. Moreover, high levels of RBM15 predicted poor clinical outcomes of cervical cancer patients. RBM15 knockdown inhibited the proliferation and epithelial-mesenchymal transition (EMT) of cervical cancer cells. RBM15 promoted the m6A modification of EZH2 as well as its protein translation. Additionally, EZH2 bound to the promoter of fibronectin 1 (FN1) and EZH2-FN1 is the cascade downstream of RBM15. Overexpressed EZH2 antagonized the effects of RBM15 knockdown and promoted the aggressiveness of cervical cancer. In summary, RBM15/EZH2/FN1 signaling cascade induces the proliferation and EMT of cervical cancer. Therefore, RBM15/EZH2/FN1 signaling may be a promising strategy for cervical cancer.
{"title":"RBM15-mediated N6-methyl adenosine (m6A) modification of EZH2 drives the epithelial-mesenchymal transition of cervical cancer","authors":"Ruixue Wang, Wenhua Tan","doi":"10.1615/critreveukaryotgeneexpr.2024052205","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024052205","url":null,"abstract":"RBM15 functions as an oncogene in multi-type cancers. However, the report on the roles of RBM15 in cervical cancer is limited. The purpose of this study was to investigate the potentials of RBM15 in cervical cancer. RT-qPCR was conducted to determine mRNA levels. Western was carried out to detect protein expression. CCK-8 and colony formation assays were carried out to determine cell proliferation. Scratch and transwell assays were carried out to determine cell migration and invasion. MeRIP assay was conducted to determine N6-methyl adenosine (m6A) levels. Luciferase assay was conducted to verify the m6A sites of EZH2 and binding sites between cc and promoter of FN1. ChIP assay was conducted to verify the interaction between EZH2 and FN1. RBM15 was upregulated in cervical cancer tissues and cells. Moreover, high levels of RBM15 predicted poor clinical outcomes of cervical cancer patients. RBM15 knockdown inhibited the proliferation and epithelial-mesenchymal transition (EMT) of cervical cancer cells. RBM15 promoted the m6A modification of EZH2 as well as its protein translation. Additionally, EZH2 bound to the promoter of fibronectin 1 (FN1) and EZH2-FN1 is the cascade downstream of RBM15. Overexpressed EZH2 antagonized the effects of RBM15 knockdown and promoted the aggressiveness of cervical cancer. In summary, RBM15/EZH2/FN1 signaling cascade induces the proliferation and EMT of cervical cancer. Therefore, RBM15/EZH2/FN1 signaling may be a promising strategy for cervical cancer.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"25 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139764428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SIAH2 function as an oncogene in various cancer. However, the roles of SIAH2 in hepatocellular carcinoma (HCC) is still unknown. This study aimed to investigate the roles of SIAH2 in HCC. Immunohistochemistry was used determine SIAH2 and ACSL4 expression in clinical samples. RT-qPCR was used to determine mRNA expression. Western blot assay was applied for determined protein expression. Ubiquitination assay was conducted for determining ubiquitination of ACSL4. Xenograft experiment was applied for determining tumor growth. Flow cytometry was applied to determine the functions of CD8+ T cells. SIAH2 expression was overexpressed in HCC tumors. High levels of SIAH2 predicted poor outcomes. However, SIAH2 knockdown promoted the proliferation of CD8+ T cells as well as promoted the ferroptosis of tumor cells, inhibiting tumor growth in HCC. ACSL4 is required for CD8+ T cell-mediated ferroptosis of HCC cells. However, SIAH2 induced ubiquitination of ACSL4 and inhibited its expression. Arachidonic acid and MEN synergistically promoted the immune checkpoint blockade. SIAH2-mediated inactivation of CD8+ T cells inhibits the ferroptosis of HCC. Therefore, targeting SIAH2 may be a promising strategy for HCC.
SIAH2 在多种癌症中发挥着癌基因的功能。然而，SIAH2在肝细胞癌（HCC）中的作用尚不清楚。本研究旨在探讨 SIAH2 在 HCC 中的作用。研究采用免疫组化法测定临床样本中 SIAH2 和 ACSL4 的表达。RT-qPCR 用于测定 mRNA 表达。采用 Western 印迹法测定蛋白质表达。泛素化检测用于确定 ACSL4 的泛素化。异种移植实验用于确定肿瘤的生长情况。流式细胞术用于确定 CD8+ T 细胞的功能。SIAH2在HCC肿瘤中表达过高。高水平的SIAH2预示着较差的预后。然而，敲除 SIAH2 可促进 CD8+ T 细胞的增殖，并促进肿瘤细胞的铁变态反应，从而抑制 HCC 肿瘤的生长。CD8+ T细胞介导的HCC细胞铁凋亡需要ACSL4。然而，SIAH2 会诱导 ACSL4 泛素化并抑制其表达。花生四烯酸和 MEN 能协同促进免疫检查点阻断。SIAH2 介导的 CD8+ T 细胞失活抑制了 HCC 的铁凋亡。因此，靶向 SIAH2 可能是治疗 HCC 的一种有前景的策略。
{"title":"SIAH2-mediated degradation of ACSL4 inhibits the anti-tumor activity of CD8+ T cells in hepatocellular carcinoma","authors":"Fangzheng Shu, Yuhua Shi, Xiangxiang Shan, Wenzhang Zha, Rengen Fan, Wanjiang Xue","doi":"10.1615/critreveukaryotgeneexpr.2024051981","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024051981","url":null,"abstract":"SIAH2 function as an oncogene in various cancer. However, the roles of SIAH2 in hepatocellular carcinoma (HCC) is still unknown. This study aimed to investigate the roles of SIAH2 in HCC. Immunohistochemistry was used determine SIAH2 and ACSL4 expression in clinical samples. RT-qPCR was used to determine mRNA expression. Western blot assay was applied for determined protein expression. Ubiquitination assay was conducted for determining ubiquitination of ACSL4. Xenograft experiment was applied for determining tumor growth. Flow cytometry was applied to determine the functions of CD8+ T cells. SIAH2 expression was overexpressed in HCC tumors. High levels of SIAH2 predicted poor outcomes. However, SIAH2 knockdown promoted the proliferation of CD8+ T cells as well as promoted the ferroptosis of tumor cells, inhibiting tumor growth in HCC. ACSL4 is required for CD8+ T cell-mediated ferroptosis of HCC cells. However, SIAH2 induced ubiquitination of ACSL4 and inhibited its expression. Arachidonic acid and MEN synergistically promoted the immune checkpoint blockade. SIAH2-mediated inactivation of CD8+ T cells inhibits the ferroptosis of HCC. Therefore, targeting SIAH2 may be a promising strategy for HCC.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"14 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139764553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1615/critreveukaryotgeneexpr.2024052773
Jinbin Wu, Yaoming Yan
Inflammation-mediated dysfunction of cardiomyocytes is the main cause of diabetic cardiomyopathy (DCM). The present study aimed to investigate the roles of SIAH1 in DCM. RT-qPCR was conducted to detect mRNA levels. ELISA was performed to detect cytokine release. Western blot was used to detect protein expression. LDH assay was used to determine cytotoxicity. In vitro ubiquitination assay was applied to determine the ubiquitination of IκB-α. TUNEL assay was conducted to determine cell death. Flow cytometry was applied for determining cardiomyocyte pyroptosis. The results showed that SIAH1 was overexpressed in human inflammatory cardiomyopathy. High expression of SIAH1 was associated with inflammatory response. SIAH1 was also overexpressed lipopolysaccharide (LPS)-induced inflammatory cardiomyopathy model in vitro. However, SIAH1 knockdown suppressed the inflammatory-related pyroptosis of cardiomyocytes. SIAH1 promoted the ubiquitination of IκB-α and activation of NF-κB signaling, which promoted the pyroptosis of cardiomyocytes. In conclusion, SIAH1 exacerbated the progression of human inflammatory cardiomyopathy via inducing the ubiquitination of IκB-α and activation of NF-κB signaling. Therefore, SIAH1/IκB-α/NF-κB signaling may be a potential target for human inflammatory cardiomyopathy.
{"title":"SIAH1 promotes the pyroptosis of cardiomyocytes in diabetic cardiomyopathy via regulating IκB-α/NF-κB signaling","authors":"Jinbin Wu, Yaoming Yan","doi":"10.1615/critreveukaryotgeneexpr.2024052773","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024052773","url":null,"abstract":"Inflammation-mediated dysfunction of cardiomyocytes is the main cause of diabetic cardiomyopathy (DCM). The present study aimed to investigate the roles of SIAH1 in DCM. RT-qPCR was conducted to detect mRNA levels. ELISA was performed to detect cytokine release. Western blot was used to detect protein expression. LDH assay was used to determine cytotoxicity. In vitro ubiquitination assay was applied to determine the ubiquitination of IκB-α. TUNEL assay was conducted to determine cell death. Flow cytometry was applied for determining cardiomyocyte pyroptosis. The results showed that SIAH1 was overexpressed in human inflammatory cardiomyopathy. High expression of SIAH1 was associated with inflammatory response. SIAH1 was also overexpressed lipopolysaccharide (LPS)-induced inflammatory cardiomyopathy model in vitro. However, SIAH1 knockdown suppressed the inflammatory-related pyroptosis of cardiomyocytes. SIAH1 promoted the ubiquitination of IκB-α and activation of NF-κB signaling, which promoted the pyroptosis of cardiomyocytes. In conclusion, SIAH1 exacerbated the progression of human inflammatory cardiomyopathy via inducing the ubiquitination of IκB-α and activation of NF-κB signaling. Therefore, SIAH1/IκB-α/NF-κB signaling may be a potential target for human inflammatory cardiomyopathy.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"23 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139969659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1615/CritRevEukaryotGeneExpr.2023048085
Jonathan D Leavenworth, Nabiha Yusuf, Quamarul Hassan
K homology-type splicing regulatory protein (KSRP) is emerging as a key player in cancer biology, and immunology. As a single-strand nucleic acid binding protein it functions in both transcriptional and post-transcriptional regulation, while facilitating multiple stages of RNA metabolism to affect proliferation and control cell fate. However, it must interact with other proteins to determine the fate of its bound substrate. Here we provide an minireview of this important regulatory protein and describe its complex subcellular functions to affect RNA metabolism, stability, miRNA biogenesis and maturation, stress granule function, metastasis, and inflammatory processes.
{"title":"K-Homology Type Splicing Regulatory Protein: Mechanism of Action in Cancer and Immune Disorders.","authors":"Jonathan D Leavenworth, Nabiha Yusuf, Quamarul Hassan","doi":"10.1615/CritRevEukaryotGeneExpr.2023048085","DOIUrl":"10.1615/CritRevEukaryotGeneExpr.2023048085","url":null,"abstract":"<p><p>K homology-type splicing regulatory protein (KSRP) is emerging as a key player in cancer biology, and immunology. As a single-strand nucleic acid binding protein it functions in both transcriptional and post-transcriptional regulation, while facilitating multiple stages of RNA metabolism to affect proliferation and control cell fate. However, it must interact with other proteins to determine the fate of its bound substrate. Here we provide an minireview of this important regulatory protein and describe its complex subcellular functions to affect RNA metabolism, stability, miRNA biogenesis and maturation, stress granule function, metastasis, and inflammatory processes.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"34 1","pages":"75-87"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41221436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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