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

Cited 17 time in Web of Science Cited 18 time in Scopus

Min, Jimin; Han, Tae-Su; Sohn, Yoojin; Shimizu, Takahiro; Choi, Boram; Bae, Seong-Woo; Hur, Keun; Kong, Seong-Ho; Suh, Yun-Suhk; Lee, Hyuk-Joon; Kim, Jang-Seong; Min, Jeong-Ki; Kim, Woo-Ho; Kim, V. Narry; Choi, Eunyoung; Goldenring, James R.; Yang, Han-Kwang

Issue Date
Springer Verlag
Gastric Cancer, Vol.23 No.4, pp.600-613
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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  • College of Natural Sciences
  • School of Biological Sciences
Research Area Molecular Biology & Genetics


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