Tumor-suppressive miRNA-135a inhibits breast cancer cell proliferation by targeting ELK1 and ELK3 oncogenes.

Abstract

Breast cancer is the most common malignant disease amongst women. miRNAs are small, non-coding RNAs that regulate gene expression, thus have the potential to play an important role during cancer development. Emerging evidence shows that miR-135a is down-regulated in breast cancer cells, but the functional roles of miR-135a in breast cancer cells remains unexplored. For this purpose, we investigated the expression of miR-135a in breast cancer cells and explored its functional role during breast cancer progression. In vitro study showed that miR-135a may be a novel tumor suppressor. Further studies showed that transcription factors ELK1 and ELK3 are direct target genes of miR-135a that modulates the suppressive function of miR-135a in breast cancer cells. Induced expression of miR-135a significantly downregulated the expression of ELK1 and ELK3 both at mRNA and protein levels. Furthermore, the effect of miR-135a in MCF-7 and T47D cells was investigated by the overexpression of miR-135a mimics. In vitro, induced expression of miR-135a in breast cancer cells inhibited cell Proliferation and clongenicity. Moreover, a luciferase activity assay revealed that miR-135a could directly target the 3'-untranslated region (3' UTRS) of ELK1 and ELK3 oncogenes. In addition, rescue experiment demonstrated that the promoted cell growth by transcription factors ELK1 and ELK3 was attenuated by the over-expression of miR-135a. Our study demonstrates that miR-135a regulates cell proliferation in breast cancer by targeting ELK1 and ELK3 oncogenes, and suggests that miR-135a potentially can act as a tumor suppressor.