MiR-135a promotes growth and invasion of colorectal cancer via metastasis suppressor 1 in vitro

Acta Biochim Biophys Sin (Shanghai). 2012 Oct;44(10):838-46. doi: 10.1093/abbs/gms071.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that participate in the spatiotemporal regulation of messenger RNA and protein synthesis. Aberrant miRNA expression leads to developmental abnormalities and diseases. The miR-135a is considered to be oncogenic; however, the functions and mechanisms of miR-135a in colorectal cancer (CRC) are largely unknown. Thus, we investigated the functions and mechanisms of miR-135a, especially its relationship with the metastasis suppressor 1 (MTSS1) gene in CRC. The expression of miR-135a was determined by real-time polymerase chain reaction, while its effect on cell proliferation, migration, and invasion was determined by MTT, without and with matrigel, respectively. The expression of MTSS1 was detected by western blot analysis. It was found that miR-135a expression was higher in human CRC samples than in non-tumor control tissue. Using SW480 and SW620 CRC cell lines, increased proliferation was observed in response to miR-135a. We also demonstrated that miR-135a promoted mobility and invasion via transwell assay with and without Matrigel, respectively, of CRC cells. In contrast, inhibition of miR-135a reduced their proliferative and invasive capability. MTSS1 was identified as a candidate target gene of miR-135a by luciferase report assay. Western blot analysis showed that the expression of MTSS1 was regulated by miR-135a overexpression and knockdown. Similarly, miR-135a-mediated cell mobility and invasion were reduced after MTSS1 was knocked down by small interfering RNA. These data indicated that miR-135a promotes the growth and invasion of CRC cells, at least partially, through targeting MTSS1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation*
  • Cell Survival / genetics
  • Collagen
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Drug Combinations
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Laminin
  • Male
  • MicroRNAs / genetics*
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Proteoglycans
  • Real-Time Polymerase Chain Reaction

Substances

  • Drug Combinations
  • Laminin
  • MIRN135 microRNA, human
  • MTSS1 protein, human
  • MicroRNAs
  • Microfilament Proteins
  • Neoplasm Proteins
  • Proteoglycans
  • matrigel
  • Collagen