RNA m<SUP>5</SUP>C modification upregulates E2F1 expression in a manner dependent on YBX1 phase separation and promotes tumor progression in ovarian cancer

作者全名："Liu, Xiaoyi; Wei, Qinglv; Yang, Chenyue; Zhao, Hongyan; Xu, Jie; Mobet, Youchaou; Luo, Qingya; Yang, Dan; Zuo, Xinzhao; Chen, Ningxuan; Yang, Yu; Li, Li; Wang, Wei; Yu, Jianhua; Xu, Jing; Liu, Tao; Yi, Ping"

作者地址："[Liu, Xiaoyi; Wei, Qinglv; Yang, Chenyue; Zhao, Hongyan; Xu, Jie; Mobet, Youchaou; Yang, Dan; Zuo, Xinzhao; Chen, Ningxuan; Yang, Yu; Xu, Jing; Liu, Tao; Yi, Ping] Chongqing Med Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Chongqing 401120, Peoples R China; [Wei, Qinglv] Chongqing Med Univ, Childrens Hosp, Chongqing Key Lab Child Infect & Immun, Chongqing 400014, Peoples R China; [Luo, Qingya] Army Med Univ, Southwest Hosp, Dept Pathol, Chongqing 400038, Peoples R China; [Li, Li] Army Med Univ, Daping Hosp, Dept Obstet & Gynecol, Chongqing 400042, Peoples R China; [Wang, Wei] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Yu, Jianhua] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA 91010 USA"

通信作者："Liu, T; Yi, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Chongqing 401120, Peoples R China."

来源：EXPERIMENTAL AND MOLECULAR MEDICINE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001177217400006

JCR分区：Q1

影响因子：9.5

年份：2024

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期号：　

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文献类型：Article; Early Access

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摘要："5-Methylcytosine (m(5)C) is a common RNA modification that modulates gene expression at the posttranscriptional level, but the crosstalk between m(5)C RNA modification and biomolecule condensation, as well as transcription factor-mediated transcriptional regulation, in ovarian cancer, is poorly understood. In this study, we revealed that the RNA methyltransferase NSUN2 facilitates mRNA m(5)C modification and forms a positive feedback regulatory loop with the transcription factor E2F1 in ovarian cancer. Specifically, NSUN2 promotes m(5)C modification of E2F1 mRNA and increases its stability, and E2F1 binds to the NSUN2 promoter, subsequently reciprocally activating NSUN2 transcription. The RNA binding protein YBX1 functions as the m5C reader and is involved in NSUN2-mediated E2F1 regulation. m(5)C modification promotes YBX1 phase separation, which upregulates E2F1 expression. In ovarian cancer, NSUN2 and YBX1 are amplified and upregulated, and higher expression of NSUN2 and YBX1 predicts a worse prognosis for ovarian cancer patients. Moreover, E2F1 transcriptionally regulates the expression of the oncogenes MYBL2 and RAD54L, driving ovarian cancer progression. Thus, our study delineates a NSUN2-E2F1-NSUN2 loop regulated by m(5)C modification in a manner dependent on YBX1 phase separation, and this previously unidentified pathway could be a promising target for ovarian cancer treatment."

基金机构：National Natural Science Foundation of China (National Science Foundation of China)

基金资助正文：No Statement Available