Microrna-30C-2-3P Regulates Er Stress and Induces Apoptosis in Ovarian Cancer Cells Underlying Er Stress Publisher



Barez SR¹ ; Attar AM¹ ; Aghaei M¹
Source: EXCLI Journal Published:2021

Abstract

Ovarian cancer is a common gynecologic cancer with a high rate of recurrence, drug resistance, and mortality, thereby necessitating novel molecular target therapies. Ovarian cancer as a solid tumor has constantly been chal-lenged by endoplasmic reticulum stress (ERS). Currently, XBP1 as a therapeutic target in solid tumors plays a key role in adaptation to ERS. Single-stranded RNAs usually modulate posttranscriptional of the gene activity. miR-30c-2-3p has been demonstrated to inhibit the expression of XBP1. Here, we evaluated the effect of miR-30c-2-3p on controlling XBP1-CHOP-BIM and its apoptotic effects on ovarian cancer cell lines during ERS. The ER stress was assessed using Thioflavin T staining in OVCAR3 and SKOV3 cells. The expression of ER stress genes was measured by QRT-PCR. The protein levels of XBP1(s), BIP/GRP78, CHOP, and BIM were evaluated using Western blotting. Cell viability and apoptosis in STF-083010 and Tunicamycin (Tm) co-treated cells were evalu-ated using BrdU, MTT, Annexin V-FITC/PI staining, and caspase-12 and -3 activities assays. We found that miR-30c-2-3p significantly decreased the folding capacity of ER, leading to ERS intensification (P<0.05). Additionally, the Western blot analysis showed the modest up-regulation of CHOP and BIM with pro-apoptotic activity and down-regulation of the BIP protein. Furthermore, mimic miR-30c-2-3p transfection not only decreased cell pro-liferation but also induced cell death in ovarian cancer cells in response to the Tm-treatment. Our results indicated that the apoptotic pathway was induced possibly through activation of caspases -12 and -3 and elevation of the Bax/Bcl-2 ratio. Overall, the present paper adds new evidence to the possible treatment of miR-30c-2-3p via im-peding the XBP1 transcription in ovarian cancer cells provoking apoptotic pathways by XBP1/CHOP/BIM medi-ators. © 2021, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.