MicroRNA-197-3p to counteract chemoresistance in ovarian cancer via COL4A6 inhibition.

Abstract

221 Background: Collagen type IV alpha 6 (COL4A6) is overexpressed in ovarian cancer, where its elevated levels contribute to tumor progression, chemoresistance, and poor clinical outcomes. Although dysregulation of microRNAs (miRNAs) is well documented in epithelial ovarian carcinoma (EOC), whether they contribute to the control of COL4A6 expression has not been clearly established. Methods: miR-197-3p levels in EOC tissues and cell lines were measured using real-time PCR. Functional experiments, including assays for cell viability and cisplatin responsiveness, were conducted to determine the biological role of miR-197-3p in ovarian cancer cells. Candidate genes regulated by miR-197-3p were examined and confirmed through luciferase reporter testing together with protein-level verification by western blotting. Associations between miR-197-3p expression and clinical outcomes were subsequently examined. Results: miR-197-3p expression was markedly reduced in both EOC tissues and cell lines. Restoring miR-197-3p levels suppressed ovarian cancer cell viability and increased their responsiveness to cisplatin. Mechanistic studies demonstrated that miR-197-3p directly targets COL4A6, and modification of this regulatory axis alters cellular survival and chemoresistance. Clinically, diminished miR-197-3p expression correlated with advanced disease stage, suboptimal chemotherapy response, earlier recurrence, and poorer overall and progression-free survival. Conclusions: miR-197-3p inhibits EOC progression and reduces chemoresistance by directly targeting COL4A6, underscoring its promise as a potential therapeutic candidate.