Snail-regulated MiR-375 inhibits migration and invasion of gastric cancer cells by targeting JAK2

PLoS One. 2014 Jul 23;9(7):e99516. doi: 10.1371/journal.pone.0099516. eCollection 2014.

Abstract

MicroRNAs (miRNAs) have been reported to play a critical role in cancer invasion and metastasis. Our previous study showed that miR-375 frequently downregulated in gastric cancer suppresses cell proliferation by targeting Janus kinase 2 (JAK2). Here, we further found that the expression level of miR-375 is significantly decreased in metastatic gastric cancer tissues compared with the non-metastasis controls. Ectopic expression of miR-375 inhibits the migration and invasion of gastric cancer cells partially by targeting JAK2. Furthermore, miR-375 expression is negatively regulated by the metastasis associated transcription factor Snail, which directly binds to the putative promoter of miR-375. Moreover, overexpression of Snail can partially reverse the inhibition of gastric cancer cell migration caused by miR-375. Taken together, these data suggest that miR-375 may be negatively regulated by Snail and involved in gastric cancer cell migration and invasion potentially by targeting JAK2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Janus Kinase 2 / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Snail Family Transcription Factors
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Wound Healing / genetics

Substances

  • MIRN375 microRNA, human
  • MicroRNAs
  • Snail Family Transcription Factors
  • Transcription Factors
  • Janus Kinase 2

Grants and funding

This work was supported by Natural Scientific Foundation of China (31301149, 31071221, 31190063, 31125017 and 31100975), Ministry of Science and Technology of China (2013CB945603, 2012CB945004 and (2011CBA01001), Ministry of Education of China (20110101110103 and (20130101120001), Natural Scientific Foundation of Zhejiang Province, China (LQ13H160013, LQ14H160003, Z2100247 and Y2100106), the 111 Project (B13026), The Fundamental Research Funds for the Central Universities (2014QNA7015) and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.