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您的检索式：作者名="Yuanfa Feng"
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| 1 | Metformin escape in prostate cancer by activating the PTGR1 transcriptional program through a novel super-enhancer显示文摘The therapeutic efficacy of metformin in prostate cancer(PCa)appears uncertain based on various clinical trials.Metformin treatment failure may be attributed to the high frequency of transcriptional dysregulation,which leads to drug resistance.However,the underlying mechanism is still unclear.In this study,we found evidences that metformin resistance in PCa cells may be linked to cell cycle reactivation.Super-enhancers(SEs),crucial regulatory elements,have been shown to be associated with drug resistance in various cancers.Our analysis of SEs in metformin-resistant(MetR)PCa cells revealed a correlation with Prostaglandin Reductase 1(PTGR1)expression,which was identified as significantly increased in a cluster of cells with metformin resistance through single-cell transcriptome sequencing.Our functional experiments showed that PTGR1 overexpression accelerated cell cycle progression by promoting progression from the G0/G1 to the S and G2/M phases,resulting in reduced sensitivity to metformin.Additionally,we identified key transcription factors that significantly increase PTGR1 expression,such as SRF and RUNX3,providing potential new targets to address metformin resistance in PCa.In conclusion,our study sheds new light on the cellular mechanism underlying metformin resistance and the regulation of the SE-TFs-PTGR1 axis,offering potential avenues to enhance metformin’s therapeutic efficacy in PCa. | Jianheng Ye Shanghua Cai Yuanfa Feng Jinchuang Li Zhiduan Cai Yulin Deng Ren Liu Xuejin Zhu Jianming Lu Yangjia Zhuo Yingke Liang Jianjiang Xie Yanqiong Zhang Huichan He Zhaodong Han Zhenyu Jia Weide Zhong | 2023 | Signal Transduction and Targeted Therapy2023，8，9： | 0 |
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