期刊
GASTRIC CANCER
卷 23, 期 4, 页码 600-613出版社
SPRINGER
DOI: 10.1007/s10120-020-01052-w
关键词
miR-30a; ITGA2; Metaplasia; Gastric cancer; Tumor suppressor
资金
- Korean Health Industry Development Institute (KHIDI) - Ministry of Health AMP
- Welfare, Republic of Korea [HI14C3426, HI13C2148]
- National Research Foundation of Korea - Ministry of Science and ICT [NRF-2017R1C1B2012268]
- KRIBB Research Initiative Program
- DOD [W81XWH-17-1-0257]
- Department of Veterans Affairs [IBX000930]
- NIH [RO1 DK071590, RO1 DK101332]
- JSPS
- Vanderbilt Digestive Disease Center (NIH) [P30 DK058404]
- VA [1IS1BX003097]
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.
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