MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2

J Pathol. 2014 Mar;232(4):415-27. doi: 10.1002/path.4309.

Abstract

Colorectal cancer (CRC) is the third most common cancer in the USA. MicroRNAs play important roles in the pathogenesis of CRC. In this study, we investigated the role of miR-30b in CRC and found that its expression was significantly lower in CRC tissues than that in normal tissues. We showed that a low expression level of miR-30b was closely related to poor differentiation, advanced TNM stage and poor prognosis of CRC. Further experiments showed that over-expression of miR-30b suppressed CRC cell proliferation in vitro and tumour growth in vivo. Specifically, miR-30b promoted G1 arrest and induced apoptosis. Moreover, KRAS, PIK3CD and BCL2 were identified as direct and functional targets of miR-30b. MiR-30b directly targeted the 3'-untranslated regions of their mRNAs and repressed their expression. This study revealed functional and mechanistic links between miRNA-30b and oncogene KRAS, PIK3CD and BCL2 in the pathogenesis of CRC. MiR-30b not only plays important roles in the regulation of cell proliferation and tumour growth in CRC, but is also a potential prognostic marker or therapeutic target for CRC. Restoration of miR-30b expression may represent a promising therapeutic approach for targeting malignant CRC.

Keywords: BCL2; KRAS; PIK3CD; apoptosis; colorectal cancer; miR-30b; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Apoptosis
  • Binding Sites
  • Cell Differentiation
  • Cell Proliferation
  • Class I Phosphatidylinositol 3-Kinases
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Computational Biology
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • HCT116 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Proto-Oncogene Proteins p21(ras)
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Burden
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • 3' Untranslated Regions
  • KRAS protein, human
  • MIRN30b microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CD protein, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins