Overexpression of miR-17 in gastric cancer is correlated with proliferation-associated oncogene amplification.

Abstract

The molecular mechanism underlying microRNA (miR)-17 overexpression has not been clearly evaluated in gastric cancer. We aimed to evaluate the functional roles of miR-17 in gastric cancer and test its viability as a therapeutic target. We conducted comparative genomic hybridization and expression array analyses on human gastric cancer tissue samples, as well as evaluating the functional roles of miR-17 in gastric cancer cell lines and transgenic mice. miR-17 overexpression in gastric cancer patients was associated with copy number gain of proliferation-associated oncogenes such as MYC, CCNE1, ERBB2, and FGFR2. Copy number gain of MIR17HG gene (13q31.3) was rare, with an overall frequency of 2% in gastric cancers (1 of 51). miR-17 knockdown suppressed the monolayer and anchorage-independent growth of FGFR2-amplified KATO-III gastric cancer cells. mir-17-92 TG/TG mice overexpressing the mir-17-92 cluster under the villin promoter developed spontaneous benign tumors in the intestinal tract (log-rank P for tumor-free survival = 0.069). Taken together, miR-17 overexpression in gastric cancer was rarely associated with MIR17HG gene amplification, but correlated with proliferation-associated oncogene amplification. Therefore, miR-17-targeting approach may benefit patients with gastric cancers harboring proliferation-associated oncogene amplification.

• Authors: Dongmin Park, Seok Cheol Lee, Jun Won Park, Soo Young Cho, Hark Kyun Kim
• Journal: Pathology international (Pathol Int) Vol. 64 Issue 7 Pg. 309-14 (Jul 2014) ISSN: 1440-1827 [Electronic] Australia
• PMID: 25047501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Chemical References

• MIRN17 microRNA, human
• MicroRNAs
• Mirn17 microRNA, mouse

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Comparative Genomic Hybridization (methods)
• Gene Amplification (genetics)
• Gene Expression Regulation, Neoplastic (genetics)
• Gene Knockdown Techniques
• Humans
• Mice
• MicroRNAs (genetics)
• Stomach Neoplasms (genetics, pathology)