Adipose-Derived Mesenchymal Stem Cells Reduce miR-214-5p to Promote Ovarian Cancer Progression via the β-Catenin Pathway by Targeting PAX8.

BACKGROUND: Building on our previous work, we found that human omental adipose-derived mesenchymal stem cells (ADSCs) promote ovarian cancer growth and metastasis by inducing PAX8, a key oncogenic transcription factor in ovarian cancer. TAZ is a core downstream effector of the Hippo signaling pathway, closely associated with malignant progression in multiple tumors, and our prior work confirmed that PAX8 can stabilize TAZ protein. In this study, we aimed to further clarify how ADSCs regulate PAX8 to explore the downstream signaling pathway driving malignant progression in ovarian cancer. MATERIALS AND METHODS: Ovarian cancer cells were treated with ADSC-conditioned medium (ADSC-CM) to investigate the regulatory effect of ADSCs on miR-214-5p expression. qRT-PCR and western blot were applied to detect the levels of miR-214-5p, PAX8, β-catenin, and TAZ, so as to dissect the regulatory relationship of ADSCs/miR-214-5p/PAX8/β-catenin/TAZ. A dual-luciferase reporter assay verified the direct targeting interaction between miR-214-5p and PAX8. CCK-8 and Transwell invasion assays were conducted to assess the biological functions of the miR-214-5p/PAX8 axis in ovarian cancer progression. RESULTS: We show that ADSC treatment significantly downregulated miR-214-5p in ovarian cancer cells. Moreover, PAX8 is a direct target of miR-214-5p: knockdown or overexpression of miR-214-5p altered PAX8 expression by directly binding to PAX8 mRNA. Additionally, PAX8 stabilizes TAZ by activating the β-catenin pathway. Functionally, miR-214-5p inhibited ovarian cancer cell proliferation and invasion by downregulating PAX8. CONCLUSION: Taken together, ADSCs downregulate miR-214-5p to increase PAX8 expression, which sequentially activates the β-catenin pathway and stabilizes TAZ. This novel signaling axis is responsible for ADSC-induced ovarian cancer growth and metastasis.