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

• Main Authors: Chunxian Huang, Jinxiao Liang, Shaodan Lin, Dongyan Wang, Qingsheng Xie, Zhongqiu Lin, Tingting Yao
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-06-01
• Series: Frontiers in Oncology
• Subjects: m6A; METTL3; miR-193b; CCND1; cervical cancer
• Online Access: https://www.frontiersin.org/articles/10.3389/fonc.2021.666597/full

ObjectiveCervical 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 m6A in miR-193b silencing.MethodsCervical 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 m6A regulates miR-193b expression. Luciferase reporter assays, qRT-PCR, and Western blotting were enlisted to study the interaction between miR-193b and CCND1.ResultsOur 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 m6A methylation in cervical tumors. METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through CCND1 targeting.Conclusionsm6A associated downregulation of miR-193b promotes cervical cancer aggressiveness by targeting CCND1.