MicroRNA‑133b inhibits connective tissue growth factor in colorectal cancer and correlates with the clinical stage of the disease

Mol Med Rep. 2015 Apr;11(4):2805-12. doi: 10.3892/mmr.2014.3075. Epub 2014 Dec 10.

Abstract

Accumulating evidence indicates that dysregulation of microRNA‑133b (miR‑133b) is an important step in the development of certain types of human cancer and contributes to tumorigenesis. Altered expression of miR‑133b has been reported in colon carcinoma, but its association with clinical stage in colorectal cancer (CRC) has remained elusive. Connective tissue growth factor (CTGF), a potentially promising candidate gene for interaction with miR‑133b, was screened using microarray analysis. The expression of miR‑133b and CTGF was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The regulatory effects of miR‑133b on CTGF were evaluated using a dual‑luciferase reporter assay. CTGF was identified as a functional target of miR‑133b. The results demonstrated low expression of miR‑133b in CRC specimens with poor cell differentiation (P=0.011), lymph node metastasis (P=0.037) and advanced clinical stages (stage III or IV vs. I or II; P=0.036). Furthermore, there was a significant association between a high level of expression of CTGF mRNA and an advanced clinical stage (stage III or IV vs. I or II; P=0.015) and lymph node metastasis (P=0.034). CTGF expression was negatively regulated by miR‑133b in the human colorectum, suggesting that miR‑133b and CTGF may be candidate therapeutic targets in colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • Cluster Analysis
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Connective Tissue Growth Factor / chemistry
  • Connective Tissue Growth Factor / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • RNA Interference
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Reproducibility of Results

Substances

  • 3' Untranslated Regions
  • MIRN133 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Connective Tissue Growth Factor