Upregulation of LRRC8A by m(5)C modification-mediated mRNA stability suppresses apoptosis and facilitates tumorigenesis in cervical cancer
作者全名："Chen, Yanjie; Zuo, Xinzhao; Wei, Qinglv; Xu, Jie; Liu, Xiaoyi; Liu, Shiling; Wang, Haocheng; Luo, Qingya; Wang, Yuya; Yang, Yu; Zhao, Hongyan; Xu, Jing; Liu, Tao; Yi, Ping"
作者地址："[Chen, Yanjie; Zuo, Xinzhao; Wei, Qinglv; Xu, Jie; Liu, Xiaoyi; Wang, Haocheng; Wang, Yuya; Yang, Yu; Zhao, Hongyan; Xu, Jing; Liu, Tao; Yi, Ping] Chongqing Med Univ, Dept Obstet & Gynecol, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Liu, Shiling] Army Med Univ, Daping Hosp, Dept Obstet & Gynecol, Chongqing 400042, Peoples R China; [Luo, Qingya] Army Med Univ, Southwest Hosp, Dept Pathol, Chongqing 400038, Peoples R China; [Zhao, Hongyan] Hubei Univ Med, Inst Basic Med Sci, Shiyan 442000, Hubei, Peoples R China"
通信作者："Liu, T; Yi, P (通讯作者)，Chongqing Med Univ, Dept Obstet & Gynecol, Affiliated Hosp 3, Chongqing 401120, Peoples R China."
来源：INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
ESI学科分类：BIOLOGY & BIOCHEMISTRY
摘要："Cervical cancer (CC) is one of the most common gynecological malignancies with poor prognosis for advanced CC patients. LRRC8A is a volume-regulated anion channel protein involved in cellular homeostasis, but its role in CC remains largely unknown. In this study, we found that LRRC8A is elevated in CC and associated with poor prognosis. LRRC8A maintains cell survivals under the hypotonic condition, and promotes tumorigenesis through apoptosis suppression in vitro and in vivo. Notably, LRRC8A is upregulated by NSUN2-mediated m(5)C modification. m(5)C modified-LRRC8A mRNA is bound by the RNA binding protein YBX1 followed by the increased RNA stability. Moreover, loss of NSUN2 suppresses the proliferation and metastasis of CC cells, and NSUN2 expression is positively correlated with LRRC8A expression in CC. Altogether, our study demonstrates that the NSUN2-m(5)C-LRRC8A axis is crucial and would be a potential therapeutic target for CC."
基金机构："National Natural Science Foundation of China [32101164, 82072886]; Natural Science Foundation of Chongqing, China [CSTB2022NSCQ-MSX0897, cstc2021jcyj-bshX0055]"
基金资助正文："Acknowledgements This work was sponsored by the National Natural Science Foundation of China (32101164 and 82072886) and the Natural Science Foundation of Chongqing, China (CSTB2022NSCQ-MSX0897 and cstc2021jcyj-bshX0055) ."