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

Oncol Res. 2017 Jan 26;25(2):277-283. doi: 10.3727/096504016X14732514133203. Epub 2016 Sep 13.

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.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Proliferation / physiology*
  • Female
  • Gene Targeting* / methods
  • HEK293 Cells
  • Humans
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors / biosynthesis*
  • Kruppel-Like Transcription Factors / genetics
  • MCF-7 Cells
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics

Substances

  • KLF15 protein, human
  • KLF6 protein, human
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors
  • MicroRNAs
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • microRNA-4262 microRNA, human