Long non-coding RNA MALAT1 regulates epithelial-mesenchymal transition (EMT) and metastasis in epithelial ovarian cancer (EOC) through a competing endogenous RNA (ceRNA) mechanism involving miRNA modulation. This study aimed to elucidate the molecular pathway by which MALAT1 influences EMT and metastatic behavior via interaction with miR-200c-3p and SNAI2. MALAT1 expression was genetically manipulated in the EOC cell line SK-OV-3 by either overexpression or knockdown. Functional effects on EMT-related protein levels, cell migration, and invasion were assessed using Western blotting, wound healing, and Transwell assays, respectively. Bioinformatics analysis identified miR-200c-3p as a common target of MALAT1 and SNAI2. The MALAT1/miR-200c-3p/SNAI2 axis was further validated by dual-luciferase reporter assays and immunofluorescence staining to confirm direct molecular interactions. Overexpression of MALAT1 enhanced SK-OV-3 cell migration by 20% and invasion by 5%, accompanied by a significant increase in SNAI2 expression (P < 0.01). Conversely, MALAT1 knockdown suppressed these phenotypes. Dual-luciferase assays confirmed that miR-200c-3p directly binds to both MALAT1 and SNAI2 (P < 0.001). miR-200c-3p overexpression reduced MALAT1-driven EMT by downregulating SNAI2 (P < 0.05), whereas restoring SNAI2 reversed the inhibitory effects of MALAT1 silencing on metastasis. This protocol demonstrates that MALAT1 promotes EMT and metastasis in EOC by functioning as a ceRNA that sequesters miR-200c-3p, leading to derepression of SNAI2. The findings provide a novel mechanistic insight and identify the MALAT1/miR-200c-3p/SNAI2 axis as a potential therapeutic target to inhibit ovarian cancer metastasis.
Xu et al. (Fri,) studied this question.