Zhongsheng You, Fei Wu, Yaofeng Zheng, Hongling Yang, Jianbo Ye, Hongyi Cai, Chuangcai Luo, Yang Liu, Yiquan Ke, Xiangdong Xu
{"title":"miR-139-5p通过抑制HMG-CoA还原酶的表达激活铁下垂,从而抑制胶质瘤的进展。","authors":"Zhongsheng You, Fei Wu, Yaofeng Zheng, Hongling Yang, Jianbo Ye, Hongyi Cai, Chuangcai Luo, Yang Liu, Yiquan Ke, Xiangdong Xu","doi":"10.1038/s41420-025-02532-7","DOIUrl":null,"url":null,"abstract":"<p><p>Glioma is the most aggressive and common tumour in the central nervous system. It has been reported that miR-139-5p plays an important role in regulating tumour progression. However, whether miR-139-5p affects the progression of glioma and the specific mechanism remains to be explored. Through experiments involving down-regulation or overexpression of miR-139-5p and treatment with simvastatin (SIM), qRT-PCR and Western Blot were used to detect the expression levels of related genes. Transmission electron microscopy (TEM) and corresponding kits were used to detect the changes in ferroptosis and cholesterol content in glioma cells. RNA-seq analysis was used to explore the specific mechanism by which miR-139-5p regulates ferroptosis. Our results demonstrate that miR-139-5p expression is significantly reduced in glioma cells compared to normal glial cells and is associated with poor prognosis. Overexpression of miR-139-5p promotes ferroptosis and inhibits tumour cell proliferation by downregulating HMG-CoA reductase (HMGCR) expression, consequently hindering glioma progression. Additionally, we found a synergistic effect between miR-139-5p overexpression and SIM treatment in promoting ferroptosis in gliomas. These findings suggest that miR-139-5p could serve as a potential therapeutic target for glioma treatment, particularly in combination with SIM. This study demonstrated that miR-139-5p promoted ferroptosis in glioma cells by down-regulating HMGCR expression and cholesterol synthesis. Moreover, miR-139-5p and SIM had a synergistic effect in promoting ferroptosis to prevent glioma progression.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"245"},"PeriodicalIF":6.1000,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095534/pdf/","citationCount":"0","resultStr":"{\"title\":\"miR-139-5p activates ferroptosis by inhibiting the expression of HMG-CoA reductase to inhibit the progression of glioma.\",\"authors\":\"Zhongsheng You, Fei Wu, Yaofeng Zheng, Hongling Yang, Jianbo Ye, Hongyi Cai, Chuangcai Luo, Yang Liu, Yiquan Ke, Xiangdong Xu\",\"doi\":\"10.1038/s41420-025-02532-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Glioma is the most aggressive and common tumour in the central nervous system. It has been reported that miR-139-5p plays an important role in regulating tumour progression. 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Additionally, we found a synergistic effect between miR-139-5p overexpression and SIM treatment in promoting ferroptosis in gliomas. These findings suggest that miR-139-5p could serve as a potential therapeutic target for glioma treatment, particularly in combination with SIM. This study demonstrated that miR-139-5p promoted ferroptosis in glioma cells by down-regulating HMGCR expression and cholesterol synthesis. 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miR-139-5p activates ferroptosis by inhibiting the expression of HMG-CoA reductase to inhibit the progression of glioma.
Glioma is the most aggressive and common tumour in the central nervous system. It has been reported that miR-139-5p plays an important role in regulating tumour progression. However, whether miR-139-5p affects the progression of glioma and the specific mechanism remains to be explored. Through experiments involving down-regulation or overexpression of miR-139-5p and treatment with simvastatin (SIM), qRT-PCR and Western Blot were used to detect the expression levels of related genes. Transmission electron microscopy (TEM) and corresponding kits were used to detect the changes in ferroptosis and cholesterol content in glioma cells. RNA-seq analysis was used to explore the specific mechanism by which miR-139-5p regulates ferroptosis. Our results demonstrate that miR-139-5p expression is significantly reduced in glioma cells compared to normal glial cells and is associated with poor prognosis. Overexpression of miR-139-5p promotes ferroptosis and inhibits tumour cell proliferation by downregulating HMG-CoA reductase (HMGCR) expression, consequently hindering glioma progression. Additionally, we found a synergistic effect between miR-139-5p overexpression and SIM treatment in promoting ferroptosis in gliomas. These findings suggest that miR-139-5p could serve as a potential therapeutic target for glioma treatment, particularly in combination with SIM. This study demonstrated that miR-139-5p promoted ferroptosis in glioma cells by down-regulating HMGCR expression and cholesterol synthesis. Moreover, miR-139-5p and SIM had a synergistic effect in promoting ferroptosis to prevent glioma progression.
期刊介绍:
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.