TRIM29 functions as an oncogene in gastric cancer and is regulated by miR-185

Int J Clin Exp Pathol. 2015 May 1;8(5):5053-61. eCollection 2015.

Abstract

Tripartite motif-containing 29 (TRIM29) belongs to TRIM family of transcription factors and may function as an oncogene or a tumor suppressor depending on the tumor types. Overexpression of TRIM29 is frequently observed in gastric cancer but the underlying mechanisms remain largely unknown. In the present study, we investigated the function of TRIM29 in gastric cancer-derived cell line MGC803. RNAi-mediated silencing of TRIM29 resulted in significantly reduced cell proliferation and colony formation, as well as G1-S cell cycle arrest and apoptosis. Interestingly, expression levels of β-catenin, cyclin D1 and c-Myc were all downregulated in TRIM29 knockdown cells, indicating that TRIM29 is involved in regulating the activity of Wnt/β-catenin signaling pathway. Furthermore, based on target prediction and luciferase assay, we identified TRIM29 as a potential target of miR-185, which is frequently downregulated in gastric cancer. Over-expression of miR-185 in MGC803 cells inhibited TRIM29 expression and activity of Wnt/β-catenin signaling. Taken together, our results suggest that TRIM29 functions as an oncogene in gastric cancer and is regulated by miR-185.

Keywords: TRIM29; Wnt/β-catenin signaling; gastric cancer; miR-185.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism
  • Binding Sites
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • RNA Interference
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Wnt Signaling Pathway

Substances

  • 3' Untranslated Regions
  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MIRN185 microRNA, human
  • MicroRNAs
  • Oncogene Proteins
  • TRIM29 protein, human
  • Transcription Factors