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Pathol Int. 2014 Jul;64(7):309-14. doi: 10.1111/pin.12178.

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

Author information

1
National Cancer Center, Goyang, Gyeonggi, Korea.

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.

KEYWORDS:

amplification; gastric cancer; miR-17; mice

PMID:
25047501
DOI:
10.1111/pin.12178
[Indexed for MEDLINE]

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