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