The oncogenic role of microRNA-130a/301a/454 in human colorectal cancer via targeting Smad4 expression

PLoS One. 2013;8(2):e55532. doi: 10.1371/journal.pone.0055532. Epub 2013 Feb 5.

Abstract

Transforming growth factor (TGF)-β/Smad signaling plays an important role in colon cancer development, progression and metastasis. In this study we demonstrated that the microRNA-130a/301a/454 family is up-regulated in colon cancer tissues compared to paired adjacent normal mucosa, which share the same 3'-untranslational region (3'-UTR) binding seed sequence and are predicated to target Smad4. In colorectal cancer HCT116 and SW480 cells, overexpression of miRNA-130a/301a/454 mimics enhances cell proliferation and migration, while inhibitors of these miRNAs affect cell survival. The biological function of miRNA-130a/301a/454 on colon cancer cells is likely mediated by suppression of Smad4, and the up-regulation of the miRNAs is correlated with Smad4 down-regulation in human colon cancers. Collectively, these results suggest that miRNA-130a/301a/454 are novel oncogenic miRNAs contributing to colon tumorigenesis by regulating TGF-β/Smad signaling, which may have potential application in cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Survival / genetics
  • Cell Survival / physiology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Female
  • HCT116 Cells
  • Humans
  • Immunoblotting
  • In Vitro Techniques
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Smad4 Protein / genetics
  • Smad4 Protein / metabolism*

Substances

  • MicroRNAs
  • Smad4 Protein

Grants and funding

This project is supported by grants from the National Basic Research Programs (2012CB518103), National Natural Science Foundation of China (31100554, 31270820, 81230061, and 81121004), Nursery Foundation of PLA General Hospital (12KMM48), and Beijing Nova Program (Z12111000250000). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.