Role of miR-148a in cutaneous squamous cell carcinoma by repression of MAPK pathway

Arch Biochem Biophys. 2015 Oct 1:583:47-54. doi: 10.1016/j.abb.2015.07.022. Epub 2015 Aug 5.

Abstract

Dysregulation of miRNAs is a common feature in human cancers, but there are lack of studies on roles of miRNAs in cutaneous squamous cell carcinoma (CSCC). miR-148a, a member of the miR-148/152 family, has been found to be downregulated in different types of cancer and its role in CSCC remains unknown. The study was aimed to investigate the expression and cellular function of miR-148a in CSCC. We found that miR-148a was underexpressed in CSCC tissues and cell lines. MAP3K2, MAP3K4 and MAP3K9 were predicted as the target genes of miR-148a and the latter two genes were verified as the target genes of miR-148a in CSCC cells. Importantly, we demonstrated that the overexpression of miR-148a significantly inhibited CSCC cell proliferation and metastasis via down-regulation of MAP3K9 and MAP3K4 expression. MAP3K4 and MAP3K9 were negatively associated with the expression of miR-148a in CSCC tissues. Our results suggested indicated that miR-148a acts as a tumor suppressor of CSCC via inhibiting MAPK pathway. These results may provide a promising alterative strategy for CSCC therapy.

Keywords: CSCC; MAP3K4; MAP3K9; miR-148a.

MeSH terms

  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation
  • Humans
  • MAP Kinase Signaling System / genetics*
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology

Substances

  • MIRN148 microRNA, human
  • MicroRNAs