The Effect of SNPs in IncRNA as CeRNA on The Risk and Prognosis of Hepatocellular Carcinoma

Background Most the HCC susceptible loci identified by GWAS are located in non-coding regions, and the mechanism of action remains unclear. The objective of this study was to explore the relationship among SNPs on lncRNA that affects ceRNA mechanism and the risk and prognosis of HCC. Methods In this study, combined with multiple databases, eight lncRNA genes that affect HCC were systematically screened through the mechanism of lncRNA-mediated ceRNA, and 15 SNPs that affect miRNA binding in the eight lncRNA genes were annotated. Genotyping was conducted in 800 HCC cases and 801 healthy controls from a Han population in Northeast China to examine the genetic risk associated with HCC. Results The GG, GC and GG + GC genotypes of HOTAIR rs7958904 were found to be associated with a 0.65, 0.59 and 0.63-fold decreased HCC risk, respectively. Moreover, in the stratified analysis of clinical characteristics, HCC patients with PVT1 rs3931282 AA + GA genotypes were less prone to develop late-stage tumors. When stratified by clinical biochemical indexes, rs1134492 and rs10589312 in PVT1 and rs84557 in EGFR-AS1 showed significant associations with AST, ALT or AST/ALT ratio. In addition, the potential ceRNA regulatory axes might be affected by the five positive SNPs were constructed to explain the causes of these genetic associations. Conclusions This first study demonstrated the association of SNPs on lncRNA -mediated ceRNAs with HCC. The results provide new insights of how non-coding loci confer the interindividual differences to susceptibility and progression of HCC.