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Overexpression of miR ‐17 in gastric cancer is correlated with proliferation‐associated oncogene amplification
Author(s) -
Park Dongmin,
Lee Seok Cheol,
Park Jun Won,
Cho Soo Young,
Kim Hark Kyun
Publication year - 2014
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/pin.12178
Subject(s) - oncogene , cancer , cancer research , microrna , gene knockdown , biology , gene duplication , cell growth , microbiology and biotechnology , gene , cell cycle , genetics
The molecular mechanism underlying micro RNA ( 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.