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

Abstract

Objective 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. Methods 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. Results 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. Conclusion 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.

LncRNA PSMA3‐AS1 promotes cell proliferation, migration, and invasion in ovarian cancer by activating the PI3K/Akt pathway via the miR‐378a‐3p/GALNT3 axis

“…Previous studies have demonstrated the close association of miR‐378a‐3p and the PI3K/Akt pathway 47,48 . However, a previous study revealed the opposite results that miR‐378a‐3p mimic increased the phosphorylation levels of PI3K and AKT, 49 which needs further exploration. Moreover, PSMA3‐AS1 overexpression rescued the decrease in p‐PI3K and p‐Akt protein levels, implying that PSMA3‐AS1 activated the PI3K/Akt pathway by upregulating GALNT3 in OC, and the effects of activation of GALNT3 mediated by PSMA3‐AS1 on the PI3K/Akt pathway were associated with miR‐378a‐3p.…”

“…Previous studies have demonstrated the close association of miR-378a-3p and the PI3K/Akt pathway. 47,48 However, a previous study revealed the opposite results that miR-378a-3p mimic increased the phosphorylation levels of PI3K and AKT, 49 PSMA3-AS1 upregulates GALNT3 expression by serving as a ceRNA against miR-378a-3p. The discovery might provide promising insight into the role of PSMA3-AS1 in OC.…”

lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells

“…In the current study, ACTA2-AS1 is bound with miR-378a-3p in GC. Previously, miR-378a-3p was reported to promote ovarian cancer progression by targeting protein disulfide-isomerase A4 (PDIA4) [ 56 ]. lncRNA ACTA2 antisense RNA 1 (ZXF1) suppresses the progression of endometrial carcinoma by interacting with miR-378a-3p to upregulate the expression of protocadherin alpha-3 [ 57 ].…”

Hypoxia-Induced miR-378a-3p Inhibits Osteosarcoma Invasion and Epithelial-to-Mesenchymal Transition via BYSL Regulation

“…Several studies have documented a strong link between miR-378a-3p function and cancer pathogenesis (Pan et al, 2019;Zheng et al, 2020). For example, overexpression of miR-378a-3p was reported to increase ovarian cancer cell development (Chanjiao et al, 2021). Moreover, breast cancer patients with low expression of miR-378a-3p in cancer tissues who were under tamoxifen treatment were found to have a weak prognosis (Ikeda et al, 2015).…”