Open Access

ARTICLE

miR-148b Functions as a Tumor Suppressor by Targeting Endoplasmic Reticulum Metallo Protease 1 in Human Endometrial Cancer Cells

Jinfeng Qu^*, Lei Zhang^†, Lanyu Li^*, Yujie Su^*

* Department of Obstetrics and Gynecology, Jinan Central Hospital, Jinan, P.R. China
† Department of Obstetrics and Gynecology, Dongying People’s Hospital, Dongying, P.R. China

Oncology Research 2019, 27(1), 81-88. https://doi.org/10.3727/096504018X15202988139874

Abstract

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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