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

Area of Science:

• Molecular Oncology
• Gastroenterology
• Cancer Biology

Background:

• Spasmolytic polypeptide-expressing metaplasia (SPEM) is a precursor to intestinal metaplasia and gastric cancer (GC).
• MicroRNA (miRNA) alterations in metaplasia and GC development remain largely unknown.
• Investigating miR-30a expression and its targets in gastric lesions is crucial for understanding GC pathogenesis.

Purpose of the Study:

• To investigate the expression patterns of miR-30a in gastric precancerous lesions and intestinal-type GC.
• To identify novel target genes of miR-30a involved in GC development.
• To elucidate the functional role of the miR-30a-ITGA2 axis in gastric carcinogenesis.

Main Methods:

• In situ hybridization and qRT-PCR were used to determine miR-30a expression in gastric tissues.
• GC cell lines were used to study miR-30a functions via induction or inhibition.
• Gene microarray, siRNA-mediated gene suppression, immunostaining, and The Cancer Genome Atlas data were employed to identify and validate miR-30a targets.

Main Results:

• miR-30a expression was down-regulated during chief cell transdifferentiation to SPEM and in early-stage GC, with sustained low levels in advanced GC.
• Integrin alpha-2 (ITGA2) was identified as a novel target gene of miR-30a.
• Ectopic expression of miR-30a or ITGA2 knockdown suppressed GC cell proliferation, migration, and tumorigenesis, with inverse correlation between miR-30a and ITGA2 levels in human GC.

Conclusions:

• miR-30a exhibits tumor-suppressive functions in GC by targeting the oncogenic ITGA2.
• ITGA2 is up-regulated in human GC, and its levels inversely correlate with miR-30a expression.
• The miR-30a-ITGA2 axis plays a significant role in the development of gastric precancerous lesions and intestinal-type GC.