microRNA-30a arbitrates intestinal-type early gastric carcinogenesis by directly targeting ITGA2

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microRNA-30a arbitrates intestinal-type early gastric carcinogenesis by directly targeting ITGA2
J Min; Tae Su Han; Y Sohn; T Shimizu; B Choi; S W Bae; K Hur; S H Kong; Y S Suh; H J Lee; Jang Seong Kim; Jeong Ki Min; W H Kim; V N Kim; E Choi; J R Goldenring; H K Yang
Bibliographic Citation
Gastric Cancer, vol. 23, no. 4, pp. 600-613
Publication Year
Background: Spasmolytic polypeptide-expressing metaplasia (SPEM) is considered a precursor lesion of intestinal metaplasia and intestinal-type gastric cancer (GC), but little is known about microRNA alterations during metaplasia and GC developments. Here, we investigate miR-30a expression in gastric lesions and identify its novel target gene which is associated with the intestinal-type GC. Methods: We conducted in situ hybridization and qRT-PCR to determine miR-30a expression in gastric tissues. miR-30a functions were determined through induction or inhibition of miR-30a in GC cell lines. A gene microarray was utilized to confirm miR-30a target genes in GC, and siRNA-mediated target gene suppression and immunostaining were performed. The Cancer Genome Atlas data were utilized to validate gene expressions. Results: We found down-regulation of miR-30a during chief cell transdifferentiation into SPEM. MiR-30a level was also reduced in the early stage of GC, and its level was maintained in advanced GC. We identified a novel target gene of miR-30a and ITGA2, and our results showed that either ectopic expression of miR-30a or ITGA2 knockdown suppressed GC cell proliferation, migration, and tumorigenesis. Levels of ITGA2 inversely correlated with levels of miR-30a in human intestinal-type GC. Conclusion: We found down-regulation of miR-30a in preneoplastic lesions and its tumor-suppressive functions by targeting ITGA2 in GC. The level of ITGA2, which functions as an oncogene, was up-regulated in human GC. The results of this study suggest that coordination of the miR-30a-ITGA2 axis may serve as an important mechanism in the development of gastric precancerous lesions and intestinal-type GC.
MetaplasiaGastric cancerTumor suppressorITGA2miR-30a
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Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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