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N(6)-Methyladenosine Associated Silencing of miR-193b Promotes Cervical Cancer Aggressiveness by Targeting CCND1

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 an...

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Detalles Bibliográficos
Autores principales: Huang, Chunxian, Liang, Jinxiao, Lin, Shaodan, Wang, Dongyan, Xie, Qingsheng, Lin, Zhongqiu, Yao, Tingting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222573/
https://www.ncbi.nlm.nih.gov/pubmed/34178650
http://dx.doi.org/10.3389/fonc.2021.666597
Descripción
Sumario: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.