This study investigated the tumor-suppressive role of miR-148b in regulating endoplasmic reticulum metalloprotease 1 (ERMP1) expression and the oxidative stress response in endometrial cancer cells. Human endometrial cancer RL95-2 cells were used and transfected with miR-148b mimic,
miR-148b inhibitor, or their scrambled negative control. Thereafter, the transfection efficiency was determined by RT-qPCR, and cell proliferation was assessed by MTT assay. The dual-luciferase reporter assay, Western blot, and RT-qPCR were conducted to determine the target gene of miR-148b.
ERMP1 is a putative target of miR-148b, and thereby the overexpression and downregulation of ERMP1 on the proliferation of RL95-2 cells were assessed. Next, the expressions of hypoxia-inducible factor 1 (HIF-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) were analyzed by Western
blot. Intracellular reactive oxygen species (ROS) was determined using dichlorofluorescin diacetate (DCFDA). Results showed that differential expression of miR-148b or ERMP1 was observed in normal endometrial tissues and endometrial cancerous tissues. Enhanced expression of miR-148b effectively
inhibited proliferation of RL95-2 cells. ERMP1 was the target of miR-148b. ERMP1 silencing obviously suppressed proliferation of RL95-2 cells. Thus, miR-148b repressed cell proliferation, likely through downregulating ERMP1. Furthermore, it was observed that miR-148b significantly decreased
expression of HIF-1 and Nrf2 by downregulating ERMP1. The intracellular ROS level was enhanced by miR-148b via downregulating ERMP1. To conclude, our results suggested that miR-148b suppressed cell proliferation and regulated the oxidative stress response in human endometrial cancer RL95-2
cells by inhibiting ERMP1.
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Keywords:
ERMP1;
Endometrial cancer cells;
HIF;
Nrf2;
Oxidative stress;
miR-148b
Document Type: Research Article
Affiliations:
1:
Department of Obstetrics and Gynecology, Jinan Central Hospital, Jinan, P.R. China
2:
Department of Obstetrics and Gynecology, Dongying People’s Hospital, Dongying, P.R. China
Publication date:
December 27, 2018
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Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
From Volume 23, Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics is Open Access under the terms of the Creative Commons CC BY-NC-ND license.
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