U/G SNP rs111904020 in 3'UTR of STAT3 regulated by miR-214 promotes hepatocellular carcinoma development in Chinese population.

STAT3 is an oncogene which mainly capable of regulating various biological characters by its transcriptional factor features driving thousands of genes. However, its upstream noncoding RNA-related regulations still remain unknown. In this study, we focused on the microRNA (miRNA)-associated single nucleotide polymorphisms (SNPs) in the 3' unstranslated region (UTR) of STAT3 to investigate the further relationship of the SNPs with miRNAs among Chinese patients with hepatocellular carcinoma (HCC). We found that patients suffering from HBV infection indicated to be the susceptible population by comparing with controls. Besides, SNP rs111904020 (U/G) in STAT3, 3'UTR was involved in the occurrence of HCC by acting as tumor promoter factors. SNP rs111904020 (U/G) could be regulated by miR-214 which caused an upregulation of STAT3. Furthermore, the carriers of G genotype was related to high expression of STAT3, and larger tumor size as well as high probability of metastasis. Moreover, the SNP of U/G was associated with poor survival and high reoccurrence of HCC with a 5-year follow-up study. In conclusion, our findings have shown that the SNP rs111904020 (U/G) in STAT3 3'UTR acted as promotion factors in the HCC development through disrupting the regulatory role of miR-214 in STAT3 expression.