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

ABSTRACT:

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 m⁶A 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 m⁶A 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 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.

Conclusions

m⁶A associated downregulation of miR-193b promotes cervical cancer aggressiveness by targeting CCND1.

SUBMITTER: Huang C

PROVIDER: S-EPMC8222573 | biostudies-literature |

REPOSITORIES: biostudies-literature

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