Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma

J Hum Genet. 2012 Jan;57(1):38-45. doi: 10.1038/jhg.2011.126. Epub 2011 Nov 17.


Analysis of the microRNA (miRNA) expression signature of lung squamous cell carcinoma (lung-SCC) revealed that the expression levels of miR-133a were significantly reduced in cancer tissues compared with normal tissues. In this study, we focused on the functional significance of miR-133a in cancer cell lines derived from lung-SCC and the identification of miR-133a-regulated novel cancer networks in lung-SCC. Restoration of miR-133a expression in PC10 and H157 cell lines resulted in significant inhibition of cell proliferation, suggesting that miR-133a functions as a tumor suppressor. We used genome-wide gene expression analysis to identify the molecular targets of miR-133a regulation. Gene expression data and web-based searching revealed several candidate genes, including transgelin 2 (TAGLN2), actin-related protein2/3 complex, subunit 5, 16kDa (ARPC5), LAG1 homolog, ceramide synthase 2 (LASS2) and glutathione S-transferase pi 1 (GSTP1). ARPC5 and GSTP1 likely represent bona fide targets as their expression is elevated in lung-SCC clinical specimens. Furthermore, transient transfection of miR-133a, repressed ARPC5 and GSTP1 mRNA and protein levels. As cell proliferation was significantly inhibited in lung-SCC cells following RNAi knock down of either gene, ARPC5 and GSTP1 may function as oncogenes in the development of lung-SCC. The identification of a tumor suppressive miRNA and the novel cancer pathways it regulates could provide new insights into potential molecular mechanisms of lung-SCC carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks / genetics*
  • Gene Silencing
  • Genes, Tumor Suppressor*
  • Genetic Association Studies
  • Glutathione S-Transferase pi / genetics
  • Glutathione S-Transferase pi / metabolism
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transfection


  • MIRN133 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Messenger
  • GSTP1 protein, human
  • Glutathione S-Transferase pi