title: 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.affiliation: National Cancer Center, Goyang, Gyeonggi, Korea.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Park
authors.forename: Seok Cheol
authors.initials: SC
authors.lastname: Lee
authors.forename: Jun Won
authors.initials: JW
authors.lastname: Park
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Cho
authors.forename: Hark Kyun
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D055028:Comparative Genomic Hybridization / Q000379:methods; D005784:Gene Amplification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C524941:MIRN17 microRNA, human; D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse
keywords: amplification; gastric cancer; miR-17; mice