The Functional SOCS3 RS115785973 Variant Regulated by MiR-4308 Promotes Gastric Cancer Development in Chinese Population

Abstract

Background/Aims: SOCS3 is tumor suppressor which has been identified as upstream of JAK/STAT3 signaling by specific kinase inhibition. However, additional regulations especially through a non-coding RNA approach were remained unknown. Methods: We performed case-control study focusing on the miRNAs associated SNPs in SOCS3 to investigate the further relationship of the SNPs with miRNAs among Chinese gastric cancer (GC) patients. Genotyping, real time PCR assay, cell transfection and the dual luciferase reporter assay were used in our study. Results: We found that patients suffering from Helicobacter pylori (H. pylori) infection indicating as susceptible population by comparing with controls. Besides, SNP rs115785973 in SOCS3 was identified as a risk factor in the occurrence of GC highly associated with poor differentiation grade, larger tumor size and metastasis. In vitro assay found that rs115785973 could be regulated by miR-4308 which caused an up-regulation of SOCS3 in patients with GA and AA genotype. Conclusion: Our findings have shown that the SNP rs115785973 in SOCS3 disrupting the regulatory role of miR-4308 in SOCS3 expression, rs115785973 in SOCS3 might act as a risk factor in the pathogenesis of GC.