AUTHOR=Huang Chunxian , Liang Jinxiao , Lin Shaodan , Wang Dongyan , Xie Qingsheng , Lin Zhongqiu , Yao Tingting 

TITLE=N6-Methyladenosine Associated Silencing of miR-193b Promotes Cervical Cancer Aggressiveness by Targeting CCND1

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.666597

DOI=10.3389/fonc.2021.666597

ISSN=2234-943X

ABSTRACT=<sec><title>Objective</title><p>Cervical cancer is a frequently encountered gynecological malignancy as a major contributor to cancer-related deaths in women. This study focuses on how miR-193b promotes cervical cancer aggressiveness as well as the role of m<sup>6</sup>A in miR-193b silencing.</p></sec><sec><title>Methods</title><p>Cervical cancer samples and the matching adjacent normal cervical tissues were used to determine the significance of miR-193b in cervical cancer. The CCK-8 assay, cell cycle analysis, qRT-PCR, Western blot assay, IHC, RIP, and xenograft models were utilized to explore the impact of miR-193b in cervical cancer and how m<sup>6</sup>A regulates miR-193b expression. Luciferase reporter assays, qRT-PCR, and Western blotting were enlisted to study the interaction between miR-193b and CCND1.</p></sec><sec><title>Results</title><p>Our study suggested that lower miR-193b expressions were strongly linked to more advanced cervical cancer stages and the presence of deeper stromal invasion. miR-193b functions as a tumor suppressor that is regulated by m<sup>6</sup>A methylation in cervical tumors. METTL3 modulates miR-193b mature process in an m<sup>6</sup>A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both <italic>in vivo</italic> and <italic>in vitro</italic> through CCND1 targeting.</p></sec><sec><title>Conclusions</title><p>m<sup>6</sup>A associated downregulation of miR-193b promotes cervical cancer aggressiveness by targeting CCND1.</p></sec>