miR-143-3p targeting LIM domain kinase 1 suppresses the progression of triple-negative breast cancer cells

Am J Transl Res. 2017 May 15;9(5):2276-2285. eCollection 2017.


Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer is one of the most aggressive types of breast cancer as it has the worst clinical outcome for patients. microRNAs are a type of small non-coding RNA and play an important role in breast cancer. The purpose of this study was to explore the potential function and mechanism of miR-143-3p in triple-negative breast cancer (TNBC). MTT and colony formation assays, the effect of miR-143-3p modulation on MDA-MB-231 cell proliferation, revealed that increased miR-143-3p expression inhibited the proliferation of MDA-MB-231 TNBC cells. Moreover, miR-143-3p overexpression inhibited the movement of MDA-MB-231 TNBC cells in wound healing and transwell assays. To identify a potential miR-143-3p target, we investigated the effect of miR-143-3p modulation on LIMK1 expression level. Increased miR-143-3p expression caused a reduction in LIMK1 mRNA and protein, suggesting that LIMK1 is a target of miR-143-3p. In addition, dual-luciferase reporter assays showed that LIMK1 is a target gene of miR-143-3p. Flow cytometry analysis indicated that miR-143-3p arrested MDA-MB-231 TNBC cells at the G0/G1 phase. The TCGA (The Cancer Genome Atlas) database demonstrated that miR-143-3p was down-regulated in breast cancer tissues compared with normal breast tissues. These data demonstrated that miR-143-3p functioned as a suppressor gene in TNBC and that miR-143 targeted therapy may be a new strategy for TNBC treatment.

Keywords: LIMK1; cell cycle; miR-143-3p; progression; triple-negative breast cancer (TNBC).