EPDR1, Which Is Negatively Regulated by miR-429, Suppresses Epithelial Ovarian Cancer Progression via PI3K/AKT Signaling Pathway

Abstract

Epithelial ovarian cancer (EOC) is the main pathological type of ovarian cancer. In this study, we found that ependymin-related 1 (EPDR1) was remarkably downregulated in EOC tissues, and low EPDR1 expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, metastasis, and poor prognosis. We confirmed that EPDR1 overexpression dramatically suppressed EOC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, EPDR1 inhibited EOC tumorigenesis and progression, at least in part, through the repression of the PI3K (Phosphoinositide 3-kinase)/AKT (AKT Serine/Threonine Kinase 1) signaling pathway. Furthermore, the expression and function of EPDR1 were regulated by miR-429, as demonstrated by luciferase reporter assays and rescue experiments. In conclusion, our study validated that EPDR1, negatively regulated by miR-429, played an important role as a tumor-suppressor gene in EOC development via inhibition of the PI3K/AKT pathway. The miR-429/EPDR1 axis might provide novel therapeutic targets for individualized treatment of EOC patients in the future.

Hypoxia-induced miR-181a-5p up-regulation reduces epirubicin sensitivity in breast cancer cells through inhibiting EPDR1/TRPC1 to activate PI3K/AKT signaling pathway

“…The study suggested that miRNAs may be regulated by the tumor microenvironment, including hypoxia, and are involved in regulating hypoxia-induced responses [31]. Interestingly, EPDR1 expression is reduced in hypoxic BC cells and several studies have shown that its expression is regulated by miRNAs [26,27]. In this study, it was hypothesized that the reduction of EPDR1 might be associated with hypoxia-induced miRNAs.…”

“…In contrast, EPDR1 exerts inhibitory effects in ovarian cancer and BC. Zhao et al confirmed that EPDR1 was downregulated in epithelial ovarian cancer (EOC) tissues and its overexpression significantly inhibited the proliferation, migration, and invasion of EOC cells and associated with the inhibition of PI3K/AKT signaling pathway [26]. Liu et al verified the similar oncogenic role of EPDR1 in ovarian cancer [27].…”

“…Zhang et al found that TRPC1 inhibited proliferation, migration, invasion, and EMT of MCF-7 cells through inhibition of PI3K/AKT signaling pathway [18]. Zhao et al reported that EPDR1 inhibited ovarian cancer cell proliferation, invasion, and migration through the PI3K/AKT pathway [26]. PI3K/AKT also stimulated tumorigenesis and progression [37].…”

Unraveling the Clotting Cascade in Vitamin K Deficiency Associated Comorbidities

“…ENSG00000086289 and ENSG00000133110 were found to be common between diabetes, apolipoprotein, placenta, hepatic, myocardial and prostate datasets. The gene ENSG00000086289 EPDR1 (Ependymin Related 1) may play a role in calcium-dependent cell adhesion that associates various types of cancer includes (15)(16)(17)(18) and the gene ENSG00000133110 Periostin (POSTN) encodes a secreted extracellular matrix protein that functions in tissue development and regeneration, including wound healing, and ventricular remodeling following myocardial infarction. Further it binds to integrins to support adhesion and migration of epithelial cells that plays a role in cancer stem cell maintenance and metastasis (19)(20)(21).…”