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1篇 您的检索式:作者名="Yonghuang Tan"
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1N6-methyladenosine facilitates mitochondrial fusion of colorectal cancer cells via induction of GSH synthesis and stabilization of OPA1 mRNA显示文摘Mitochondria undergo fission and fusion that are critical for cell survival and cancer development,while the regulatory factors for mitochondrial dynamics remain elusive.Herein we found that RNA m^(6)A accelerated mitochondria fusion of colorectal cancer(CRC)cells.Metabolomics analysis and function studies indicated that m^(6)A triggered the generation of glutathione(GSH)via the upregulation of RRM2B-a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential.This in turn resulted in the mitochondria fusion of CRC cells.Mechanistically,m^(6)A methylation of A1240 at 3'UTR of RRM2B increased its mRNA stability via binding with IGF2BP2.Similarly,m^(6)A methylation of A2212 at the coding sequence(CDS)of OPA1-an essential GTPase protein for mitochondrial inner membrane fusion-also increased mRNA stability and triggered mitochondria fusion.Targeting m^(6)A through the methyltransferase inhibitor STM2457 or the dm^(6)ACRISPR system significantly suppressed mitochondria fusion.In vivo and clinical data confirmed the positive roles of the m^(6)A/mitochondrial dynamics in tumor growth and CRC progression.Collectively,m^(6)A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression,which facilitated cancer cell growth and CRC development.Jiawang Zhou Haisheng Zhang Ke Zhong Lijun Tao Yu Lin Guoyou Xie Yonghuang Tan You Wu Yunqing Lu Zhuojia Chen Jiexin Li Xin Deng Qin Peng Zigang Li Hongsheng Wang 2024National Science Review2024,11,3:0
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