MiR‑302d‑3p regulates the viability, migration and apoptosis of breast cancer cells through regulating the TMBIM6‑mediated ERK signaling pathway.

Abstract

MicroRNAs (miRs/miRNAs) play important roles in the occurrence, metastasis and prognosis of multiple types of cancers. However, the specific role of miR-302d-3p and its underlying mechanism in breast cancer (BC) have not yet been reported. The present study aimed to identify the role of miR-302D-3p in BC and its potential mechanism using BC cell lines MCF7 and MDA-MB-231 and normal breast epithelial cell MCF-10A. Cancer and paracancerous tissue from patients with BC were also used. Reverse transcription-quantitative PCR was performed to detect the expression of miR-302d-3p and transmembrane Bax inhibitor motif containing 6 (TMBIM6). Dual-luciferase reporter assays verified the binding sites of miR-302d-3p and TMBIM6. Immunohistochemistry was used to measure the expression of TMBIM6. Cell transfection techniques were used to overexpress or interfere with miR-302d-3p and TMBIM6. A Cell Counting Kit-8 assay was performed to detect cell viability, and migration was measured using a wound healing assay. Apoptosis was detected by flow cytometry. The expression levels of apoptosis-related proteins and pathway-related proteins were detected by western blotting. The expression of miR-302d-3p in BC cell lines was found to be downregulated. It was also demonstrated that miR-302d-3p could inhibit cell viability and migration and promote apoptosis. The expression of TMBIM6 in BC cell lines and tissues was upregulated. Upregulated miR-302d-3p was shown to inhibit viability and migration, and promote apoptosis by targeting TMBIM6, during which extracellular signal-regulated kinase (ERK) and its phosphorylation were inhibited in the ERK signaling pathway in cells. Overall, the present study demonstrated that miR-302d-3p could regulate the viability, migration and apoptosis of BC cells through regulating TMBIM6-mediated ERK signaling pathway.