Upregulation of microRNA-143 reverses drug resistance in human breast cancer cells via inhibition of cytokine-induced apoptosis inhibitor 1

摘要

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1), originally termed anamorsin, is an anti-apoptotic molecule that acts as a downstream effector of the receptor tyrosine kinase-Ras signaling pathway. Overexpression of CIAPIN1 contributes to multidrug resistance (MDR) and microRNA (miR)-143 is typically considered a tumor suppressor in breast cancer. The present study aimed to evaluate the therapeutic potential of miR-143 as a treatment for drug-resistant breast cancer via the downregulation of CIAPIN1 in vitro. The expression levels of miR-143 were measured using quantitative polymerase chain reaction and the expression levels of CIAPIN1 were detected via western blot analysis. Bioinformatic analyses was additionally conducted to search for miR-143, which may potentially target CIAPIN1. Luciferase reporter plasmids were created and used to verify direct targeting. In addition, Taxol-induced drug-resistant (TDR) breast cancer cell proliferation was evaluated using the Cell Counting Kit-8 assay in vitro. The present study identified an inverse association between miR-143 and CIAPIN1 protein expression levels in breast cancer MCF-7, MDA-MB-231 and MDA-MB-453 TDR cells. Specific targeting sites for miR-143 in the 3'-untranslated region of the CIAPIN1 gene were identified, which exhibit the ability to regulate CIAPIN1 expression. It was revealed that the repression of CIAPIN1 via miR-143 suppressed the proliferation of breast cancer TDR cells. The findings of the present study verified the role of miR-143 as a tumor suppressor in breast cancer MDR via inhibition of CIAPIN1 translation.