miR-6745-TIMP1 axis inhibits cell growth and metastasis in gastric cancer

Aging (Albany NY). 2021 Nov 14;13(21):24402-24416. doi: 10.18632/aging.203688. Epub 2021 Nov 14.

Abstract

Tissue inhibitor matrix metalloproteinase 1 (TIMP1) has been reported to act as a tumor oncogene in colon cancer. However, little is known about the biological role of TIMP1 in gastric cancer. In this study, we found that the expression of TIMP1 in GC tissues was upregulated compared with the normal gastric tissues. TIMP1 was confirmed as a direct target of miR-6745 and silencing TIMP1 mimicked the effects of miR-6745 in GC cells. Further mechanism studies have shown that miR-6745 inhibits the Wnt/β-catenin pathway by targeting TIMP1, thereby inhibiting cell proliferation, migration and invasion. In addition, through the analysis of GC tissues, a negative correlation between miR-6745 and TIMP1 was found in 42 GC tissues. Our findings indicate that the miR-6745-TIMP1 axis regulates Wnt/βcatenin signaling and participates in GC tumorigenesis and provide a potential therapeutic target for preventing GC progression.

Keywords: TIMP1; Wnt/β-catenin pathway; gastric cancer; miR-6745; oncogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Metastasis / genetics
  • Stomach / metabolism
  • Stomach / pathology
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / mortality
  • Stomach Neoplasms* / pathology
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*
  • Wnt Signaling Pathway

Substances

  • MicroRNAs
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1