Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2020-07, Vol.23 (4), p.600-613

Ort / Verlag

Singapore: Springer Singapore

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.