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

Abstract

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.

Role of m6A modification in female infertility and reproductive system diseases

“…Interestingly, the m6A modification of pyruvate dehydrogenase kinase 4 is mediated by METTL3.Via binding with YTHDF1 and IGF2BP3, the translation of m6A modified PDK4 mRNA is enhanced, promoting the glycolysis of cancer cells, resulting in the growth and progression of CC [73]. A recent study reveals a different mechanism, METTL3 can promote CC aggressiveness by repressing the activity of miR-193b, which can regulate the expression of "CCND1" positively [74].…”

The Emerging Role of N6-Methyladenosine RNA Methylation as Regulators in Cancer Therapy and Drug Resistance

“…In the work of Huang et al , blockade of METTL3 in CC decreases the miR-193b expression and increases pri-miR-193b expression. The subsequent evidence proves that METTL3 modulates miR-193b mature process by promoting pri-miR-193b m 6 A methylation level ( Huang et al, 2021c ). A new study has revealed that METTL3 increases mature miR-126-5p by the m 6 A modification of pri-miR-126-5p in OC ( Bi et al, 2021 ).…”

Emerging Roles of m6A RNA Methylation Regulators in Gynecological Cancer

“…miR-193b, as a tumor suppressor, is regulated by the m 6 A methylation regulator METTL3 in cervical cancer. miR-193b inhibits the occurrence and development of cervical cancer by targeting CCND1 (69). Currently, studies on how m 6 A regulates miRNA expression in cervical cancer are relatively few, and more studies are still required to further reveal the regulatory mechanism of m 6 A in miRNA.…”