The interplay between microRNA‐21 and endothelin receptor B (EDNRB) in gastric cancer

Abstract

BackgroundMicroRNAs (miRs) are short noncoding RNA species that bind to mRNAs reducing the expression of corresponding proteins. Endothelins (ET 1‐3) are involved in vasoconstriction, angiogenesis, mitogenesis and apoptosis acting through the endothelin receptors EDNRA and EDNRB.Methods7 normal gastric (N) and 3 gastric cancer (GC) tissues were used for microRNA arrays. Global miR profiles were analyzed by Significance Analysis of Microarrays. MiR results were confirmed by qRT‐PCR on additional 72 gastric tissues. TargetScan identified EDNRB as a putative miR‐21 target. The EDNRB expression was evaluated by qRT‐PCR on all 82 gastric tissues. MKN28 GC cells were transfected with miR‐21 inhibitor (mir21i) and EDNRB level was assessed by western blotting.ResultsThe array data showed a 6‐fold miR‐21 upregulation in GC vs. N. qRT‐PCR confirmed the miR‐21 upregulation GC (p=0.011). qRT‐PCR also showed that EDNRB expression was 1.9 times lower in GC (p=0.015) vs. N, suggesting that EDNRB may function as a tumor suppressor, potentially downregulated by miR‐21. Confirming this hypothesis, miR‐21 inhibitor (miR21i) enhanced EDNRB protein in the MKN28 cells (Fig.1).Conclusionour data confirm miR‐21 overexpression in a large cohort of GC and indicate, for the first time, that EDNRB is a miR‐21 target in GC. Our findings suggest that miR‐21 plays an etiologic role in GC partly through EDNRB regulation. Lastly, EDNRB may deserve further study as a tumor suppressor in GC.