RNA Editing Enzyme ADAR1 Regulates METTL3 in an Editing Dependent Manner to Promote Breast Cancer Progression via METTL3/ARHGAP5/YTHDF1 Axis

作者全名："Li, Yi; Wang, Ning-Xi; Yin, Chuan; Jiang, Shan-Shan; Li, Jia-Chu; Yang, Sheng-Yong"

作者地址："[Li, Yi; Wang, Ning-Xi; Yin, Chuan; Jiang, Shan-Shan; Yang, Sheng-Yong] Chongqing Med Univ, Coll Basic Med, Mol Med & Canc Res Ctr, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China; [Li, Jia-Chu] Chongqing Med Univ, Dept Oncol, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Yang, SY (通讯作者)，Chongqing Med Univ, Coll Basic Med, Mol Med & Canc Res Ctr, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:000851147000001

JCR分区：Q2

影响因子：5.6

年份：2022

卷号：23

期号：17

开始页：　

结束页：　

文献类型：Article

关键词：ADAR1; METTL3; breast cancer; ARHGAP5; YTHDF1

摘要："A-to-I RNA editing and m(6)A modification are two of the most prevalent types of RNA modifications controlling gene expression in mammals and play very important roles in tumorigenesis and tumor progression. However, the functional roles and correlations of these two RNA modifications remain to be further investigated in cancer. Herein, we show that ADAR1, an A-to-I RNA-editing enzyme, interacts with METTL3 and increases its protein level to promote the proliferation, migration and invasion of breast cancer cells through a mechanism connecting ADAR1, METTL3 and YTHDF1. We show that both ADAR1 and METTL3 are upregulated in breast cancer samples, and ADAR1 positively correlates with METTL3; ADAR1 edits METTL3 mRNA and changes its binding site to miR532-5p, leading to increased METTL3 protein, which further targets ARHGAP5, recognized by YTHDF1. Additionally, we show that loss of ADAR1 significantly inhibits breast cancer growth in vivo. Collectively, our findings identify the ADAR1-METTL3 axis as a novel, important pathway that connects A-to-I editing and m(6)A RNA modifications during breast cancer progression."

基金机构："National Natural Science Foundation of China [81872444, 81602159]; Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0238, cstc2016jcyjA0054]; Science and Technology Planning Project of Yuzhong District, Chongqing City [20170109]"

基金资助正文："This research was supported by the National Natural Science Foundation of China grants 81872444 (S.-Y.Y.) and 81602159 (Y.L.), the Natural Science Foundation of Chongqing grants cstc2021jcyj-msxmX0238 (S.-Y.Y.) and cstc2016jcyjA0054 (Y.L.) and the Science and Technology Planning Project of Yuzhong District, Chongqing City, grant 20170109 (S.-Y.Y.)."