Pub Date : 2024-09-01DOI: 10.1615/critreveukaryotgeneexpr.2024054404
Weizhen Huang, Jun Li, Siwei Zhou, Yi Li, Xia Yuan
Extensive research has recently been conducted to investigate the regulating impact of exosomal circular RNAs (circRNAs) in throughout the development of multiple malignancies. Nevertheless, there is still much to learn about the biological roles and underlying mechanisms of exosomal circRNAs in colorectal cancer (CRC). Exosomes (exo) were isolated from blood samples and CRC cells by differential centrifugation. In addition, the competitive endogenous RNA (ceRNA) mechanism of circ_001860 in CRC was determined through Starbase and dual-luciferase reporter gene experiments. Gain and loss of function experiments verified the regulatory effect of circ_001860/miR-582-5p/ZEB1 on the malignant phenotype of CRC cells. The therapeutic effect of circ_001860 on CRC xenograft tumor model was explored through mouse experiment. Circ_001860 was significantly enriched in exo isolated from CRC blood samples and CRC cells. Circ_001860 can be transported into CRC cells via exo. Through competitive binding to miR-582-5p, circ_001860 increased ZEB1, thereby facilitating tumor formation in vivo as well as stimulating CRC cell proliferation and metastasis in vitro. Through the miR-582-5p/ZEB1 axis, exosomal circ_001860 enhanced the advancement of CRC. This finding may offer non-invasive biomarkers for clinical screening and diagnosis of CRC patients.
{"title":"Exosomal circ_001860 promotes colorectal cancer progression through miR-582-5p/ZEB1 axis","authors":"Weizhen Huang, Jun Li, Siwei Zhou, Yi Li, Xia Yuan","doi":"10.1615/critreveukaryotgeneexpr.2024054404","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024054404","url":null,"abstract":"Extensive research has recently been conducted to investigate the regulating impact of exosomal circular RNAs (circRNAs) in throughout the development of multiple malignancies. Nevertheless, there is still much to learn about the biological roles and underlying mechanisms of exosomal circRNAs in colorectal cancer (CRC). Exosomes (exo) were isolated from blood samples and CRC cells by differential centrifugation. In addition, the competitive endogenous RNA (ceRNA) mechanism of circ_001860 in CRC was determined through Starbase and dual-luciferase reporter gene experiments. Gain and loss of function experiments verified the regulatory effect of circ_001860/miR-582-5p/ZEB1 on the malignant phenotype of CRC cells. The therapeutic effect of circ_001860 on CRC xenograft tumor model was explored through mouse experiment. Circ_001860 was significantly enriched in exo isolated from CRC blood samples and CRC cells. Circ_001860 can be transported into CRC cells via exo. Through competitive binding to miR-582-5p, circ_001860 increased ZEB1, thereby facilitating tumor formation in vivo as well as stimulating CRC cell proliferation and metastasis in vitro. Through the miR-582-5p/ZEB1 axis, exosomal circ_001860 enhanced the advancement of CRC. This finding may offer non-invasive biomarkers for clinical screening and diagnosis of CRC patients.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190734","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 : 2024-09-01DOI: 10.1615/critreveukaryotgeneexpr.2024054273
Pietro G Signorile, Alfonso Baldi, Rosa Viceconte, Emma Carraturo, Maria Rosaria Boccellino, Mario Fordellone, Marco Montella
Endometriosis is a chronic inflammatory pathology estrogen-dependent. It is a condition affecting 5%–10% of women of reproductive age worldwide. Recent evidence indicating an embryological origin of endometriosis has provided new insights into its pathogenesis and potential therapeutic approaches. In this study, we compared the immunohistochemical expression of extracellular matrix molecules involved in the interaction between epithelium and stroma in endometriotic lesions and normal endometrial tissue. A total of 41 cases were analyzed. We examined the immunohistochemical expression of Chondroitin sulfate proteoglycan 4 (CSPG4), Keratan sulfate, Chondroitin sulfate (CS-56), Hyaluronic acid, and Heparan sulfate (HEP). Our results showed higher expression of CSPG4 and CS-56 in epithelial endometriosis samples compared to normal endometrial tissue, while HEP, Keratan sulfate, and Hyaluronic acid showed decreased expression in epithelial endometriosis samples relative to normal endometrial tissue. Additionally, endometriotic stroma exhibited more frequent low intensity of Hyaluronic acid and HEP compared to normal endometrial stroma. Investigating the levels of these molecules in eutopic and ectopic endometrial tissues enables the identification of potential therapeutic targets and the development of novel treatments aimed at disrupting the adhesive and invasive properties of endometriotic lesions.
子宫内膜异位症是一种依赖雌激素的慢性炎症性病变。全世界有 5%-10%的育龄妇女患有此病。最近有证据表明，子宫内膜异位症起源于胚胎学，这为我们了解其发病机制和潜在的治疗方法提供了新的视角。在这项研究中，我们比较了子宫内膜异位症病变和正常子宫内膜组织中参与上皮和基质相互作用的细胞外基质分子的免疫组化表达。我们检测了硫酸软骨素蛋白多糖 4（CSPG4）、硫酸角叉菜胶、硫酸软骨素（CS-56）、透明质酸和硫酸肝素（HEP）的免疫组化表达。我们的研究结果表明，与正常子宫内膜组织相比，上皮性子宫内异位症样本中 CSPG4 和 CS-56 的表达量较高，而 HEP、硫酸角叉菜胶和透明质酸在上皮性子宫内异位症样本中的表达量较正常子宫内膜组织有所下降。此外，与正常子宫内膜基质相比，子宫内膜异位症基质中透明质酸和 HEP 的表达强度更低。研究这些分子在异位和异位子宫内膜组织中的水平有助于确定潜在的治疗靶点，并开发旨在破坏子宫内膜异位症病变的粘附性和侵袭性的新型疗法。
{"title":"Glycosaminoglycans (GAGs) adenogenesis factors: immunohistochemical espression in endometriosis tissues compared to the endometrium","authors":"Pietro G Signorile, Alfonso Baldi, Rosa Viceconte, Emma Carraturo, Maria Rosaria Boccellino, Mario Fordellone, Marco Montella","doi":"10.1615/critreveukaryotgeneexpr.2024054273","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024054273","url":null,"abstract":"Endometriosis is a chronic inflammatory pathology estrogen-dependent. It is a condition affecting 5%–10% of women of reproductive age worldwide. Recent evidence indicating an embryological origin of endometriosis has provided new insights into its pathogenesis and potential therapeutic approaches. In this study, we compared the immunohistochemical expression of extracellular matrix molecules involved in the interaction between epithelium and stroma in endometriotic lesions and normal endometrial tissue.\u0000A total of 41 cases were analyzed. We examined the immunohistochemical expression of Chondroitin sulfate proteoglycan 4 (CSPG4), Keratan sulfate, Chondroitin sulfate (CS-56), Hyaluronic acid, and Heparan sulfate (HEP).\u0000Our results showed higher expression of CSPG4 and CS-56 in epithelial endometriosis samples compared to normal endometrial tissue, while HEP, Keratan sulfate, and Hyaluronic acid showed decreased expression in epithelial endometriosis samples relative to normal endometrial tissue. Additionally, endometriotic stroma exhibited more frequent low intensity of Hyaluronic acid and HEP compared to normal endometrial stroma.\u0000Investigating the levels of these molecules in eutopic and ectopic endometrial tissues enables the identification of potential therapeutic targets and the development of novel treatments aimed at disrupting the adhesive and invasive properties of endometriotic lesions.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224865","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 : 2024-08-01DOI: 10.1615/critreveukaryotgeneexpr.2024054463
Ling Li, Yueyan Wang, Lang Gao, Shunying Wu, Ying Jin
This study aimed to investigate the effects of curcumin-carbon dot conjugates (CUR-CD) on periodontitis. Porphyromonas gingivalis lipopolysaccharide (LPS) was used to establish periodontitis mode in vivo and in vitro. Histological analysis was conducted using HE staining. BMP2 and RUNX2 expression was determined using immunohistochemistry. mRNA levels were detected using RT-qPCR. Cytokine release was determined using ELISA assay. Osteogenic differentiation was detected using ALP staining. The results showed that CUR-CD inhibited the inflammatory response, as well as promoted bone healing in vivo and osteogenic differentiation in vitro. Moreover, CUR-CD downregulated METTL3, which inhibited m6A modification of IRE1α and downregulated IRE1α expression. However, overexpression of IRE1α reversed the effects of CUR-CD, stimulating inflammatory response and inhibiting bone healing and osteogenic differentiation. Collectively, CUR-CD inhibits the progression of periodontitis via downregulating IRE1α. Therefore, CUR-CD may be an alternative strategy for periodontitis.
{"title":"Curcumin-carbon dots suppress periodontitis via regulating METTL3/IRE1α signaling","authors":"Ling Li, Yueyan Wang, Lang Gao, Shunying Wu, Ying Jin","doi":"10.1615/critreveukaryotgeneexpr.2024054463","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024054463","url":null,"abstract":"This study aimed to investigate the effects of curcumin-carbon dot conjugates (CUR-CD) on periodontitis. Porphyromonas gingivalis lipopolysaccharide (LPS) was used to establish periodontitis mode in vivo and in vitro. Histological analysis was conducted using HE staining. BMP2 and RUNX2 expression was determined using immunohistochemistry. mRNA levels were detected using RT-qPCR. Cytokine release was determined using ELISA assay. Osteogenic differentiation was detected using ALP staining. The results showed that CUR-CD inhibited the inflammatory response, as well as promoted bone healing in vivo and osteogenic differentiation in vitro. Moreover, CUR-CD downregulated METTL3, which inhibited m6A modification of IRE1α and downregulated IRE1α expression. However, overexpression of IRE1α reversed the effects of CUR-CD, stimulating inflammatory response and inhibiting bone healing and osteogenic differentiation. Collectively, CUR-CD inhibits the progression of periodontitis via downregulating IRE1α. Therefore, CUR-CD may be an alternative strategy for periodontitis.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141937817","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}
Hepatocellular carcinoma (HCC) is one of the most malignant solid tumors worldwide. Long non-coding RNAs (lncRNAs) are the key factor in the pathogenesis of HCC. This study aimed to investigate the roles of lncRNA FTX in HCC. mRNA levels were detected using RT-qPCR. Protein expression was determined using western blot. cellular functions were determined using CCK-8 and PI staining assay. RNA fluorescent in situ hybridization (FISH) assay was conducted to analyze the location of lncRNA FTX and DNMT1. RNA pulldown, RNA immunoprecipitation (RIP), and chromatin-immunoprecipitation (ChIP) assays were used to ascertain the involved mechanisms. We found that FTX was downregulated in HCC patients, which was associated with poor prognosis. Moreover, DNMT1-mediated methylation of FTX promoter inhibited its expression. Interestingly, overexpression of FTX promoted the ferroptosis of HCC cells. FTX sponged miR-374b-3p to upregulate TFRC expression. However, downregulation of miR-374b-3p or overexpression of TFRC alleviated the effects of FTX knockdown and promoted the survival of HCC cells. In conclusion, DNMT1-dependent DNA methylation of FTX promotes the development of HCC through regulating miR-374b-3p/TFRC axis. Therefore, DNMT1/FTX/miR-374b-3p/TFRC axis may be a potential target for HCC.
{"title":"DNMT1-dependent DNA methylation of lncRNA FTX inhibits the ferroptosis of hepatocellular carcinoma","authors":"Sunfu Fan, Chaodan Shao, Shengnan Jia, Dafei Xie, Bingqi Yu","doi":"10.1615/critreveukaryotgeneexpr.2024054376","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024054376","url":null,"abstract":"Hepatocellular carcinoma (HCC) is one of the most malignant solid tumors worldwide. Long non-coding RNAs (lncRNAs) are the key factor in the pathogenesis of HCC. This study aimed to investigate the roles of lncRNA FTX in HCC. mRNA levels were detected using RT-qPCR. Protein expression was determined using western blot. cellular functions were determined using CCK-8 and PI staining assay. RNA fluorescent in situ hybridization (FISH) assay was conducted to analyze the location of lncRNA FTX and DNMT1. RNA pulldown, RNA immunoprecipitation (RIP), and chromatin-immunoprecipitation (ChIP) assays were used to ascertain the involved mechanisms. We found that FTX was downregulated in HCC patients, which was associated with poor prognosis. Moreover, DNMT1-mediated methylation of FTX promoter inhibited its expression. Interestingly, overexpression of FTX promoted the ferroptosis of HCC cells. FTX sponged miR-374b-3p to upregulate TFRC expression. However, downregulation of miR-374b-3p or overexpression of TFRC alleviated the effects of FTX knockdown and promoted the survival of HCC cells. In conclusion, DNMT1-dependent DNA methylation of FTX promotes the development of HCC through regulating miR-374b-3p/TFRC axis. Therefore, DNMT1/FTX/miR-374b-3p/TFRC axis may be a potential target for HCC.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141551615","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 : 2024-07-01DOI: 10.1615/critreveukaryotgeneexpr.2024054308
Xinze Liu, Kaijing Sun, Lin Feng, Xin Jin, Ying Sun, Wei Wu, Changbao Chen, Xilin Wan
Colon cancer is a malignant tumor caused by a malignant lesion of the colonic mucosal epithelium, with a high incidence in recent years. Fungi substances contain polysaccharides, terpenes, flavonoids and other chemical components, and the diversity of chemical components determines the strength of its biological activity. Studies have shown that the chemical components in fungi can be used as drugs to inhibit the growth of colon cancer. All available information about the bioactivities and mechanisms of fungus extracts and compounds in colon cancer was supplied by library database and electronic search (PubMed, ScienceDirect, CNKI, Web of Science, Google Scholar, etc.). Fungi reflect significant anti colon cancer effects through effects on colon cancer cell proliferation, cell cycle, apoptosis, tumor growth and protein expression. At present, most research focus on colon cancer cells and animal models. This review is on the purpose of the inhibition effects of chemical components in fungi on colon cancer at two levels in vivo and in vitro were reviewed. All the studies demonstrated significant improvements in colorectal cancer cells and animals after the fungi substances interventions. In this review, we give a complete overview of this subject, and summarizes recent research findings about molecular mechanisms on anti colorectal cancer.
结肠癌是结肠粘膜上皮恶性病变引起的恶性肿瘤，近年来发病率较高。真菌物质中含有多糖、萜类、黄酮类等化学成分，化学成分的多样性决定了其生物活性的强弱。研究表明，真菌中的化学成分可以作为抑制结肠癌生长的药物。通过图书馆数据库和电子检索（PubMed、ScienceDirect、CNKI、Web of Science、Google Scholar 等），获得了关于真菌提取物和化合物在结肠癌中的生物活性和机制的所有可用信息。真菌通过对结肠癌细胞增殖、细胞周期、细胞凋亡、肿瘤生长和蛋白质表达的影响，体现出明显的抗结肠癌作用。目前，大多数研究都集中在结肠癌细胞和动物模型上。本综述从体内和体外两个层面综述了真菌中的化学成分对结肠癌的抑制作用。所有研究都表明，在真菌物质干预后，结直肠癌细胞和动物的情况都有明显改善。在这篇综述中，我们对这一主题进行了全面概述，并总结了有关抗结直肠癌分子机制的最新研究成果。
{"title":"A Review: The bioactivities and mechanisms of fungus extracts and compounds in colon cancer","authors":"Xinze Liu, Kaijing Sun, Lin Feng, Xin Jin, Ying Sun, Wei Wu, Changbao Chen, Xilin Wan","doi":"10.1615/critreveukaryotgeneexpr.2024054308","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024054308","url":null,"abstract":"Colon cancer is a malignant tumor caused by a malignant lesion of the colonic mucosal epithelium, with a high incidence in recent years. Fungi substances contain polysaccharides, terpenes, flavonoids and other chemical components, and the diversity of chemical components determines the strength of its biological activity. Studies have shown that the chemical components in fungi can be used as drugs to inhibit the growth of colon cancer. All available information about the bioactivities and mechanisms of fungus extracts and compounds in colon cancer was supplied by library database and electronic search (PubMed, ScienceDirect, CNKI, Web of Science, Google Scholar, etc.). Fungi reflect significant anti colon cancer effects through effects on colon cancer cell proliferation, cell cycle, apoptosis, tumor growth and protein expression. At present, most research focus on colon cancer cells and animal models. This review is on the purpose of the inhibition effects of chemical components in fungi on colon cancer at two levels in vivo and in vitro were reviewed. All the studies demonstrated significant improvements in colorectal cancer cells and animals after the fungi substances interventions. In this review, we give a complete overview of this subject, and summarizes recent research findings about molecular mechanisms on anti colorectal cancer.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141780605","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 : 2024-06-01DOI: 10.1615/critreveukaryotgeneexpr.2024053662
Zhihui Duan
MS4A3 functions as a tumor suppressor in multi-type cancer. However, the role of MS4A3 in lung cancer is still unknown. Therefore, this study aims to investigate the potential of MS4A3 in lung cancer. RT-qPCR is carried out to detect mRNA expression. CCK-8 and colony formation assay are conducted to determine cell proliferation. Tube formation assay is performed to determine angiogenesis. Flow cytometry is used to calculate apoptosis rates. JASPAR is used to determine the binding motif of THAP1. Luciferase and ChIP assay are conducted to verify that MS4A3 can interact with THAP1 to transcriptionally inactivate EGFR. MS4A3 is downregulated in non-small cell lung cancer (NSCLC) patients, which predicts poor clinical outcomes of NSCLC patients. Overexpressed MS4A3 enhances the chemosensitivity of NSCLC cells to Osimertinib. Moreover, MS4A3 suppresses the proliferation and angiogenesis and promotes the apoptosis of NSCLC cells. Moreover, MS4A3 upregulates apoptosis-related THAP1 to inactivate EGFR. However, THAP1 knockdown attenuates the effects of MS4A3 and promotes the malignant behavior of NSCLC cells. MS4A3 functions as an anti-tumor gene in NSCLC. MS4A3/THAP1/EGFR signaling enhances the chemosensitivity of lung cancer to EGFR tyrosine kinase inhibitor (TKI).
{"title":"MS4A3 promotes the chemosensitivity of lung cancer via THAP1/EGFR pathways","authors":"Zhihui Duan","doi":"10.1615/critreveukaryotgeneexpr.2024053662","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024053662","url":null,"abstract":"MS4A3 functions as a tumor suppressor in multi-type cancer. However, the role of MS4A3 in lung cancer is still unknown. Therefore, this study aims to investigate the potential of MS4A3 in lung cancer. RT-qPCR is carried out to detect mRNA expression. CCK-8 and colony formation assay are conducted to determine cell proliferation. Tube formation assay is performed to determine angiogenesis. Flow cytometry is used to calculate apoptosis rates. JASPAR is used to determine the binding motif of THAP1. Luciferase and ChIP assay are conducted to verify that MS4A3 can interact with THAP1 to transcriptionally inactivate EGFR. MS4A3 is downregulated in non-small cell lung cancer (NSCLC) patients, which predicts poor clinical outcomes of NSCLC patients. Overexpressed MS4A3 enhances the chemosensitivity of NSCLC cells to Osimertinib. Moreover, MS4A3 suppresses the proliferation and angiogenesis and promotes the apoptosis of NSCLC cells. Moreover, MS4A3 upregulates apoptosis-related THAP1 to inactivate EGFR. However, THAP1 knockdown attenuates the effects of MS4A3 and promotes the malignant behavior of NSCLC cells. MS4A3 functions as an anti-tumor gene in NSCLC. MS4A3/THAP1/EGFR signaling enhances the chemosensitivity of lung cancer to EGFR tyrosine kinase inhibitor (TKI).","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141253651","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 : 2024-06-01DOI: 10.1615/critreveukaryotgeneexpr.2024054011
Yanhong Chen, Jia Huang
FTO is aberrantly expressed in brain disorders. However, the roles of FTO in neonatal hypoxic-ischemic brain injury (HIE) are still unclear. This study aims to investigate the potential of FTO in neonatal HIE. Oxygen-glucose deprivation (OGD) was used to establish HIE in vitro. mRNA levels were detected by RT-qPCR. Protein expression was detected by western blot. The levels of MDA, SOD, Fe2+ and GSH was detected by specific kit. m6A sites were analyzed using SRAMP and further verify by MeRIP assay. Cell proliferation was determined by CCK-8. Cell death was determined by PI staining. FTO was downregulated in patients with neonatal HIE and OGD-treated neurons. Moreover, FTO mRNA expression was decreased in ferroptosis inducer, especially FAC. However, overexpression of FTO inhibited the ferroptosis of neurons. Moreover, FTO-mediated m6A modification of FTH1 suppressed its mRNA expression and stability, inhibiting its protein expression. However, overexpression of FTH1 abrogated the effects of FTO and promoted the ferroptosis of neurons. In summary, FTO functions as a protective role in neonatal HIE via inhibiting FTH1 signaling. Thence, targeting may be a promising strategy for FTO neonatal HIE.
FTO 在脑部疾病中异常表达。然而，FTO在新生儿缺氧缺血性脑损伤（HIE）中的作用仍不清楚。本研究旨在探讨 FTO 在新生儿 HIE 中的潜在作用。通过 RT-qPCR 检测 mRNA 水平。蛋白表达采用免疫印迹法检测。使用 SRAMP 分析 m6A 位点，并通过 MeRIP 检测进一步验证。用 CCK-8 测定细胞增殖。细胞死亡通过 PI 染色测定。新生儿 HIE 患者和经 OGD 处理的神经元中 FTO 下调。此外，FTO mRNA 在铁变态反应诱导剂（尤其是 FAC）中表达减少。然而，过量表达 FTO 可抑制神经元的铁突变。此外，FTO 介导的 FTH1 m6A 修饰抑制了其 mRNA 的表达和稳定性，抑制了其蛋白质的表达。然而，过量表达 FTH1 可减弱 FTO 的作用，促进神经元的铁凋亡。总之，FTO 通过抑制 FTH1 信号转导在新生儿 HIE 中发挥保护作用。因此，靶向治疗可能是治疗 FTO 新生儿 HIE 的一种有前途的策略。
{"title":"FTO-mediated m6A modification of FTH1 inhibits ferroptosis of neurons in neonatal cerebral hypoxic ischaemia","authors":"Yanhong Chen, Jia Huang","doi":"10.1615/critreveukaryotgeneexpr.2024054011","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024054011","url":null,"abstract":"FTO is aberrantly expressed in brain disorders. However, the roles of FTO in neonatal hypoxic-ischemic brain injury (HIE) are still unclear. This study aims to investigate the potential of FTO in neonatal HIE. Oxygen-glucose deprivation (OGD) was used to establish HIE in vitro. mRNA levels were detected by RT-qPCR. Protein expression was detected by western blot. The levels of MDA, SOD, Fe2+ and GSH was detected by specific kit. m6A sites were analyzed using SRAMP and further verify by MeRIP assay. Cell proliferation was determined by CCK-8. Cell death was determined by PI staining. FTO was downregulated in patients with neonatal HIE and OGD-treated neurons. Moreover, FTO mRNA expression was decreased in ferroptosis inducer, especially FAC. However, overexpression of FTO inhibited the ferroptosis of neurons. Moreover, FTO-mediated m6A modification of FTH1 suppressed its mRNA expression and stability, inhibiting its protein expression. However, overexpression of FTH1 abrogated the effects of FTO and promoted the ferroptosis of neurons. In summary, FTO functions as a protective role in neonatal HIE via inhibiting FTH1 signaling. Thence, targeting may be a promising strategy for FTO neonatal HIE.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141501318","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 : 2024-06-01DOI: 10.1615/critreveukaryotgeneexpr.2024054038
Liang Xu, Sunfu Fan, Dafei Xie, Yongqi Yu
KDM6A is abnormally expressed in various cancer. This study aimed to investigate the potential of KDM6A in pancreatic cancer (PC). mRNA expression was calculated by RT-qPCR. Protein expression was detected by western blot. Cell viability was measured by CCK-8 assay. Cell angiogenesis was determined by tube formation assay. Cell migration and invasion were determined by transwell assay. We found that KDM6A was upregulated in PC patients and cells. Interestingly, KDM6A deficiency inhibited the proliferation and angiogenesis of PC cells. Moreover, KDM6A knockdown suppressed the migration and invasion of PC cells. Additionally, KDM6A upregulated the expression of LAMP3 via driving demethylation of H3K27me3. Overexpression of LAMP3 reversed the effects of KDM6A knockdown and contributed to the angiogenesis and aggressiveness of PC cells. In summary, KDM6A-mediated demethylation of H3K27me3 promotes the transcription of LAMP3, resulting the angiogenesis and aggressiveness of PC. Therefore, targeting KDM6A may be an anti-angiogenetic strategy for PC.
KDM6A 在多种癌症中异常表达。本研究旨在探讨 KDM6A 在胰腺癌（PC）中的潜在作用。蛋白表达用 Western 印迹法检测。细胞活力通过 CCK-8 试验测定。通过试管形成试验测定细胞血管生成。细胞迁移和侵袭通过透孔试验进行测定。我们发现 KDM6A 在 PC 患者和细胞中上调。有趣的是，KDM6A 缺乏会抑制 PC 细胞的增殖和血管生成。此外，KDM6A 基因敲除抑制了 PC 细胞的迁移和侵袭。此外，KDM6A通过驱动H3K27me3的去甲基化上调LAMP3的表达。LAMP3的过度表达逆转了KDM6A敲除的效果，并促进了PC细胞的血管生成和侵袭性。综上所述，KDM6A介导的H3K27me3去甲基化促进了LAMP3的转录，导致了PC的血管生成和侵袭性。因此，靶向 KDM6A 可能是 PC 的一种抗血管生成策略。
{"title":"KDM6A promotes angiogenesis, migration, and invasion of pancreatic cancer via activating LAMP3","authors":"Liang Xu, Sunfu Fan, Dafei Xie, Yongqi Yu","doi":"10.1615/critreveukaryotgeneexpr.2024054038","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024054038","url":null,"abstract":"KDM6A is abnormally expressed in various cancer. This study aimed to investigate the potential of KDM6A in pancreatic cancer (PC). mRNA expression was calculated by RT-qPCR. Protein expression was detected by western blot. Cell viability was measured by CCK-8 assay. Cell angiogenesis was determined by tube formation assay. Cell migration and invasion were determined by transwell assay. We found that KDM6A was upregulated in PC patients and cells. Interestingly, KDM6A deficiency inhibited the proliferation and angiogenesis of PC cells. Moreover, KDM6A knockdown suppressed the migration and invasion of PC cells. Additionally, KDM6A upregulated the expression of LAMP3 via driving demethylation of H3K27me3. Overexpression of LAMP3 reversed the effects of KDM6A knockdown and contributed to the angiogenesis and aggressiveness of PC cells. In summary, KDM6A-mediated demethylation of H3K27me3 promotes the transcription of LAMP3, resulting the angiogenesis and aggressiveness of PC. Therefore, targeting KDM6A may be an anti-angiogenetic strategy for PC.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141528894","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 : 2024-06-01DOI: 10.1615/critreveukaryotgeneexpr.2024054162
Jennifer Toner, Jonathan Gordon, Haley Greenyer, Peter Kaufman, Janet Stein, Gary Stein, Jane Lian
The RUNX2 transcription factor was discovered as an essential transcriptional regulator for commitment to osteoblast lineage cells and bone formation. Expression of Runx2 in other tissues, such as breast, prostate and lung, has been linked to oncogenesis, cancer progression and metastasis. In this study, we sought to determine the extent of Runx2 involvement in other tumors using a pan–cancer analysis strategy. We correlated RUNX2 expression and clinical-pathological parameters in human cancers by interrogating using publicly available multiparameter clinical data. Our analysis demonstrated that altered RUNX2 expression or function is associated with several cancer types from different tissues. We identified that 3 tumor types were associated with increased RUNX2 expression and decreased expression of RUNX2 is associated with 4 other cancer types. Our pan-cancer analysis for RUNX2 revealed numerous other discoveries for RUNX2 regulation of different cancers identified in each of the pan-cancer databases we used. Both up and down regulation of RUNX2 was observed during progression of specific types of cancers in promoting the distinct types of cancers.
{"title":"Runx2 as a Prognostic Factor in Human Cancers","authors":"Jennifer Toner, Jonathan Gordon, Haley Greenyer, Peter Kaufman, Janet Stein, Gary Stein, Jane Lian","doi":"10.1615/critreveukaryotgeneexpr.2024054162","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024054162","url":null,"abstract":"The RUNX2 transcription factor was discovered as an essential transcriptional regulator for commitment to osteoblast lineage cells and bone formation. Expression of Runx2 in other tissues, such as breast, prostate and lung, has been linked to oncogenesis, cancer progression and metastasis. In this study, we sought to determine the extent of Runx2 involvement in other tumors using a pan–cancer analysis strategy. We correlated RUNX2 expression and clinical-pathological parameters in human cancers by interrogating using publicly available multiparameter clinical data. Our analysis demonstrated that altered RUNX2 expression or function is associated with several cancer types from different tissues. We identified that 3 tumor types were associated with increased RUNX2 expression and decreased expression of RUNX2 is associated with 4 other cancer types. Our pan-cancer analysis for RUNX2 revealed numerous other discoveries for RUNX2 regulation of different cancers identified in each of the pan-cancer databases we used. Both up and down regulation of RUNX2 was observed during progression of specific types of cancers in promoting the distinct types of cancers.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141192647","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}
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