MiR-4262 Promotes Proliferation and Invasion of Human Breast Cancer Cells Through Directly Targeting KLF6 and KLF15.

Abstract

miRNAs have been shown to be involved in breast cancer growth and progression. miR-4262 is a potential tumor promoter in human cancers. In this study, we first investigated the role of miR-4262 in the proliferation and invasion of human breast cancer cells. Our results showed that, compared with the adjacent tissues and MCF-10A normal breast epithelial cells, miR-4262 was markedly increased in the breast cancer tissues and five cell lines, including MDA-MB-231, MDA-MB-468, MDA-MB-435, SKBR3, and MCF-7. Then the miR-4262 mimic or oligo anta-miR-4262 was transfected into MDA-MB-231 and MCF-7 breast cancer cell lines. The results showed that the miR-4262 mimic greatly increased the miR-4262 level and the proliferation and invasion of MDA-MB-231 and MCF-7 cells. In contrast, the anta-miR-4262 had a completely opposite effect on miR-4262 expression, cell proliferation, and cell invasion in MDA-MB-231 and MCF-7 cells. Moreover, bioinformatics and luciferase reporter gene assays confirmed that miR-4262 targeted the mRNA 3′-UTR region of KLF6 and KLF15, two characterized tumor suppressor genes. miR-4262 suppressed protein levels of KLF6 and KLF15 in MDA-MB-231 cells, and the suppression could be rescued by the transfection of pcDNA-KLF6 and -KLF15. In conclusion, miR-4262 positively regulates proliferation and invasion of human breast cancer cells via suppression of KLF6 and KLF15.