MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2

PLoS One. 2017 Dec 8;12(12):e0189490. doi: 10.1371/journal.pone.0189490. eCollection 2017.

Abstract

MicroRNAs (miRNAs) are important regulators of pathobiological processes in various cancer. In the present study, we demonstrated that miR-93 expression was significantly up-regulated in gastric cancer tissues compared with that in matched normal mucosal tissues. High expression of miR-93 was significantly associated with lymph node metastasis and tumor-node-metastasis (TNM) stage. Functionally, ectopic expression of miR-93 promoted cell proliferation, migration, invasion, EMT phenotypes, and repressed apoptosis and G1 cell cycle arrest in vitro, and promoted tumor formation in vivo. We further identified that tissue inhibitor of metalloproteinase 2 (TIMP2) was a direct target of miR-93 by using luciferase reporter assay, qRT-PCR, and immunoblotting assay. Furthermore, knockdown of TIMP2 with specific siRNA showed similar oncogenic effects in gastric cancer cells with that transfected with miR-93 mimics. Our findings indicated that miR-93 serves as a tumor promoter in human gastric carcinogenesis by targeting TIMP2, suggesting that miR-93 might be a promising biomarker and therapeutic target for treatment of gastric cancer.

MeSH terms

  • Humans
  • Lymphatic Metastasis*
  • MicroRNAs / physiology*
  • Neoplasm Metastasis*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism*

Substances

  • MicroRNAs
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2

Grants and funding

This study was supported by grants from National Natural Science Foundation of China (No. 81172359 and 81472747, http://www.nsfc.gov.cn). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of manuscript.