NAT10-mediated RNA acetylation enhances HNRNPUL1 mRNA stability to contribute cervical cancer progression

作者全名："Long, Yingfei; Ren, Yifei; Wei, Qinglv; Mobet, Youchaou; Liu, Yujiao; Zhao, Hongyan; Liu, Tao; Cheng, Lei; Yi, Ping"

作者地址："[Long, Yingfei; Ren, Yifei; Wei, Qinglv; Mobet, Youchaou; Liu, Yujiao; Zhao, Hongyan; Liu, Tao; Cheng, Lei; Yi, Ping] Chongqing Med Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Chongqing 401120, Peoples R China"

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

来源：INTERNATIONAL JOURNAL OF MEDICAL SCIENCES

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001051718500002

JCR分区：Q1

影响因子：3.2

年份：2023

卷号：20

期号：8

开始页：1079

结束页：1090

文献类型：Article

关键词：N4-acetylcytidine (ac4C); cervical cancer; HNRNPUL1; mRNA stability; NAT10

摘要："N4-acetylcytidine (ac4C) is a lately discovered nucleotide modification that has been shown to be closely implicated in cancer. N-acetyltransferase10(NAT10) acts as an enzyme that regulates mRNA acetylation modifications. Currently, the role of NAT10-mediated RNA acetylation modification in cervical cancer remains to be elucidated. On the basis of transcriptome analysis of TCGA and GEO open datasets (GSE52904, GSE29570, GSE122697), NAT10 is upregulated in cervical cancer tissues and correlated with poor prognosis. Knockdown of NAT10 suppressed the cell proliferation, invasion, and migration of cervical cancer cells. The in vivo oncogenic function of NAT10 was also confirmed in xenograft models. Combined RNA-seq and acRIP-seq analysis revealed HNRNPUL1 as the target of NAT10 in cervical cancer. NAT10 positively regulate HNRNPUL1 expression by promoting ac4C modification and stability of HNRNPUL1 mRNA. Furthermore, depletion of HNRNPUL1 suppressed the cell division, invasion, and migration of cervical cancer. HNRNPUL1 overexpression partially restored cellular function in cervical cancer cells with NAT10 knockdown. Thus, this study demonstrates that NAT10 contributes to cervical cancer progression by enhancing HNRNPUL1 mRNA stability via ac4C modification, and NAT10-ac4C-HNRNPUL1 axis might be a potential target for cervical cancer therapy."

基金机构："National Natural Science Foundation of China [32101164, 82072886]; Natural Science Foundation of Chongqing, China [CSTB2022 NSCQ-MSX0897]"

基金资助正文："Funding This work was sponsored by the National Natural Science Foundation of China (32101164 and 82072886) and the Natural Science Foundation of Chongqing, China (CSTB2022 NSCQ-MSX0897) ."