miR-98-3p/VEGFA axis mediates MALAT1-induced angiogenesis in ovarian tumors

The functional role of MicroRNA miR-98-3p in ovarian cancer is largely unexplored and its molecular mechanisms remain incompletely understood. In this study, we identified a novel regulatory axis involving MALAT1, miR-98-3p, and VEGFA in ovarian cancer angiogenesis. The study focuses on ovarian cancer-related proliferation and migration effects, primarily involving the angiogenesis effects of ovarian cancer. RNA sequencing following MALAT1 knockdown in HEY-T30 cells revealed significant alterations in several miRNAs, particularly miR-98-3p. Luciferase reporter assays confirmed direct binding between MALAT1 and miR-98-3p, establishing MALAT1 as a competing endogenous RNA (ceRNA) for miR-98-3p. Bioinformatic analysis and luciferase reporter assays further identified VEGFA as a direct target of miR-98-3p. Clinical database analysis demonstrated a positive correlation between MALAT1 and VEGFA expression, with elevated levels of both being significantly associated with poor overall survival in ovarian cancer patients. Functionally, both MALAT1 knockdown and miR-98-3p overexpression significantly impaired HUVEC tube formation, proliferation, and migration, which could be reversed by miR-98-3p inhibition. In vivo, miR-98-3p overexpression in subcutaneous xenografts resulted in reduced tumor volume, weight, vasculature, and blood perfusion, along with decreased expression of VEGFA, MMP2, and MMP9. These findings elucidate a MALAT1/miR-98-3p/VEGFA regulatory axis that modulates tumor angiogenesis in ovarian cancer, providing potential therapeutic targets for this malignancy.