miR-21 plays a pivotal role in gastric cancer pathogenesis and progression

Zhiyu Zhang, Zejuan Li, Caiping Gao, Ping Chen, Jianjun Chen, Wenzhong Liu, Shudong Xiao, Hong Lu

Research output: Contribution to journalArticle

397 Scopus citations

Abstract

Gastric cancer causes nearly one million deaths worldwide per year. Although Helicobacter pylori infection is the main risk factor, in about 80% or more of gastric cancers, the molecular pathway underlying H. pylori infection leading to the development of gastric cancers remains unclear. Recently accumulating evidence suggests that microRNAs (miRNAs) may regulate diverse biological processes and may be important in tumorigenesis. miR-21 has been frequently observed to be aberrantly overexpressed in various tumors. Using TaqMan quantitative real-time PCR, we confirmed that miR-21 was significantly overexpressed in human gastric cancer tissues and cell lines. Remarkably, miR-21 was also significantly overexpressed in H. pylori-infected gastric mucosa, implying that overexpression of miR-21 in gastric cancer may be due in part to H. pylori infection. More importantly, we showed that forced expression of miR-21 significantly enhanced cell proliferation and invasion in AGS cells, a human gastric cancer cell line, whereas knockdown of miR-21 by inhibitor caused a significant reduction in cell proliferation and a significant increase in apoptosis. Furthermore, we demonstrated that knockdown of miR-21 significantly decreased cell invasion and migration of AGS cells. Finally, we showed that RECK, a known tumor suppressor in gastric cancer, is a bona fide target of miR-21. Taken together, miR-21 may be important in the initiation and progression of gastric cancers as an oncomiR, likely through regulating RECK. Our findings suggest a potential regulatory pathway in which H. pylori infection upregulates expression of miR-21, which in turn downregulates RECK, and then leads to the development of gastric cancer.

Original languageEnglish (US)
Pages (from-to)1358-1366
Number of pages9
JournalLaboratory Investigation
Volume88
Issue number12
DOIs
StatePublished - Dec 2008

Keywords

  • Gastric cancer
  • H. pylori infection
  • RECK
  • miR-21

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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