期刊
FRONTIERS IN ONCOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.666597
关键词
m(6)A; METTL3; miR-193b; CCND1; cervical cancer
类别
资金
- National Natural Science Foundation of China [81972433]
- Natural Science Foundation of Guangdong Province (Doctoral Research Start-up Fund Program) [2016A030310178]
The study found that lower miR-193b expressions in cervical cancer are associated with more advanced stages of the disease and deeper stromal invasion. miR-193b functions as a tumor suppressor in cervical tumors, regulated by m(6)A methylation.
Objective 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(6)A in miR-193b silencing. Methods 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(6)A regulates miR-193b expression. Luciferase reporter assays, qRT-PCR, and Western blotting were enlisted to study the interaction between miR-193b and CCND1. Results 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(6)A methylation in cervical tumors. METTL3 modulates miR-193b mature process in an m(6)A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through CCND1 targeting. Conclusions m(6)A associated downregulation of miR-193b promotes cervical cancer aggressiveness by targeting CCND1.
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