Decreased expression of microRNA-143 and -145 in human gastric cancers

Oncology. 2009;77(1):12-21. doi: 10.1159/000218166. Epub 2009 May 12.

Abstract

Objective: Downregulation of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. We investigated the role of the miRNAs miR-143 and miR-145 in gastric cancers.

Methods: The expression levels of miR-143 and miR-145 in the samples from 43 patients with gastric cancer were determined by real-time PCR using TaqMan assay. The growth inhibitory effect was estimated by the transfection of human gastric cancer cells with the miRNA.

Results: The expression levels of miR-143 and -145 were decreased in most human gastric cancers examined, as previously reported to occur in colon tumors. The transfection of human gastric MKN-1 cells with miR-145 resulted in a greater growth inhibitory effect than that with miR-143, results which were contrary to those in colon cancers. In MKN-1 cells, an additive effect on growth inhibition was shown by the combined transfection with miR-143 and miR-145; further, higher sensitivity to 5-fluorouracil was also observed following the transfection with miR-143 or miR-145. The possible candidate target messenger RNAs of miR-145 were identified to be insulin receptor substrate-1 and beta-actin.

Conclusion: Taken together, these findings suggest that miR-143 and miR-145 act as anti-oncomirs common to gastrointestinal tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Down-Regulation
  • Female
  • Fluorouracil / therapeutic use
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / physiology*
  • Middle Aged
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Tumor Cells, Cultured

Substances

  • Antimetabolites, Antineoplastic
  • MIRN143 microRNA, human
  • MIRN145 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Fluorouracil