MicroRNA-378a-3p contributes to ovarian cancer progression through downregulating PDIA4

MicroRNAs, as essential players in tumorigenesis, have been demonstrated to have a revolutionary effect on human cancer research. Ovarian cancer is the primary reason of death among gynecologic malignancies. In view of this, it is significant to identify prognostic and predictive markers for treatment of ovarian cancer. The aim of this study was to probe into the effects of miR-378a-3p and protein disulfide-isomerase A4 (PDIA4) on the biological functions of ovarian cancer cells.

miR-378a-3p expression and PDIA4 messenger RNA expression in human ovarian cancer cells, normal human ovarian epithelial cells, and serum of both ovarian cancer patients and healthy people were detected by reverse transcription-quantitative polymerase chain reaction, and the PDIA4 protein expression was tested by Western blot analysis. Ovarian cancer OVCAR3 and SKOV3 cells were transfected or cotransfected with miR-378a-3p mimic or pcDNA3.1-PDIA4 or their negative control plasmids to explore their roles in biological functions in ovarian cancer cells. Luciferase activity and RIPA assays were implemented to validate the interaction between miR-378a-3p and PDIA4. Western blot analysis was utilized to detect phosphatidylinositol-3 kinase/serine/threonine kinase (PI3K/AKT) signaling pathway-related protein expression and their phosphate expression levels.

miR-378a-3p was elevated and PDIA4 was decreased in ovarian cancer cells and serum. In addition, miR-378a-3p mimic induced ovarian cancer cell growth, while miR-378a-3p inhibitor and pcDNA3.1-PDIA4 presented an inverse trend. pcDNA3.1-PDIA4 partially eliminated the capabilities of miR-378a-3p mimic on ovarian cancer progression. Meanwhile, miR-378a-3p was found to negatively regulate PDIA4, and miR-378a-3p mimic increased the phosphorylation levels of AKT and PI3K, while pcDNA3.1-PDIA4 exhibited an opposite tendency. Furthermore, pcDNA3.1-PDIA4 largely eliminated the functions of miR-378a-3p mimic on phosphorylation levels of AKT and PI3K.

This study provides evidences that miR-378a-3p activates PI3K/AKT signaling pathway by modulating PDIA4 expression, thereby playing a role in promoting the growth of ovarian cancer cells. This study provides novel directions for targeted therapy of ovarian cancer.