The effect of SNPs in lncRNA as ceRNA on the risk and prognosis of hepatocellular carcinoma

Abstract

Background Most susceptible loci of hepatocellular carcinoma (HCC) identified by genome-wide association studies (GWAS) are located in non-coding regions, and the mechanism of action remains unclear. The objective of this study was to explore the association of single nucleotide polymorphisms (SNPs) on long non-coding RNAs (lncRNAs) that affect competing endogenous RNAs (ceRNA) regulation mechanism with the risk and prognosis of HCC. Methods Based on a set of bioinformatics strategies, eight lncRNA genes that affect HCC through the mechanism of lncRNA-mediated ceRNA were systematically screened, and 15 SNPs that affect microRNA (miRNA) binding in these lncRNA genes were annotated. Genotyping was performed in 800 HCC cases and 801 healthy controls to examine associations of these SNPs with HCC in a northeastern Chinese Han population. Results The GG, GC and GG + GC genotypes of HOTAIR rs7958904 were associated with a 0.65, 0.59 and 0.63-fold decreased HCC risk, respectively. In addition, HCC patients with PVT1 rs3931282 AA + GA genotypes were less prone to develop late-stage cancers in a stratified analysis of clinical characteristics. When stratified by clinical biochemical indexes, rs1134492 and rs10589312 in PVT1 and rs84557 in EGFR-AS1 showed significant associations with aspartate aminotransferase (AST), alanine aminotransferase (ALT) or AST/ALT ratio in HCC patients. Furthermore, we constructed potential ceRNA regulatory axes that might be affected by five positive SNPs to explain the causes of these genetic associations. Conclusions HOTAIR rs7958904, PVT1 rs3931282, rs1134492 and rs10589312, and EGFR-AS1 rs84557 might be predictors for HCC risk or prognosis. Our results provide new insights into how SNPs on lncRNA-mediated ceRNAs confer interindividual differences to occurrence and progression of HCC.

The Intergenic Type LncRNA (LINC RNA) Faces in Cancer with In Silico Scope and a Directed Lens to LINC00511: A Step toward ncRNA Precision

“…Extracted DNA from human PDAC tissues vs. adjacent normal tissues HOTTIP rs1859168 - [177] Decreased susceptibility Extracted DNA from human blood samples 8) SNP rs7958904 in HOTAIR, SNPs rs3931282, rs1134492, and rs10589312 in Plasmacytoma variant translocation 1 (PVT1) and SNP rs84557 in Epidermal growth factor receptor-Antisense RNA 1 (EGFR-AS1) have been linked to the occurrence and prognosis of HCC through affecting their binding to different effector miRs, as listed in Table 7 [178]. HOTTIP SNPs rs2067087, rs17501292, and rs17427960 and rs4102217 in the MALAT1 lncRNA increased HCC susceptibility by the regulation of certain motifs that elevate the expression of these carcinogenic lncRNA [179].…”