Tumor-suppressive role of miR-139-5p in angiogenesis and tumorigenesis of ovarian cancer: Based on GEO microarray analysis and experimental validation

Abstract

This study clarified the possible molecular mechanisms by which the miR-139-5p/SOX4/TMEM2 axis affected angiogenesis and tumorigenesis of ovarian cancer (OC) based on GEO microarray datasets and experimental support. The expression of miR-139-5p and SOX4 was examined in clinical OC samples. Human umbilical vein endothelial cells (HUVECs) and human OC cell lines were included in vitro experiments. Tube formation assay was conducted in HUVECs. The expression of SOX4, SOX4, and VEGF in OC cells was identified using Western blot and immunohistochemistry. Luciferase assays were conducted to validate the targeting relationship between miR-139-5p and SOX4 and between SOX4 and TMEM2. A RIP assay assessed the binding of SOX4 and miR-139-5p. The impact of miR-139-5p and SOX4 on OC tumorigenesis in vivo was evaluated in nude mice. SOX4 was up-regulated, while miR-139-5p was down-regulated in OC tissues and cells. Ectopic miR-139-5p expression or SOX4 knockdown inhibited angiogenesis and tumorigenicity of OC. By targeting SOX4 in OC, miR-139-5p lowered VEGF expression, angiogenesis, and TMEM2 expression. The miR-139-5p/SOX4/TMEM2 axis also reduced VEGF expression and angiogenesis, which might curtail OC growth in vivo. Collectively, miR-139-5p represses VEGF expression and angiogenesis by targeting the transcription factor SOX4 and down-regulating TMEM2 expression, thereby impeding OC tumorigenesis.