An SNP reducing SNORD105 and PPAN expression decreases the risk of hepatocellular carcinoma in a Chinese population

J Clin Lab Anal. 2021 Dec;35(12):e24095. doi: 10.1002/jcla.24095. Epub 2021 Nov 5.

Abstract

Background: With hepatocellular carcinoma (HCC) becoming a heavy disease burden in China, it is particular to reveal its pathological mechanism. Recent researches have indicated that small nucleolar RNAs (snoRNAs) may be involved in various cancers including HCC. Polymorphisms within snoRNAs may affect its function or expression level, and even its host gene, then produce series of effects related to itself or its host gene.

Methods: The association of the single nucleotide polymorphism (SNP) rs2305789 in SNORD105 with HCC susceptibility was evaluated in two independent case-control sets (712 HCC and 801 controls). The contribution of rs2305789 to HCC risk was investigated using case-control, genotype-phenotype correlation analysis, and functional assays.

Results: The SNP rs2305789 was significantly associated with a decreased risk of HCC in both case-control sets (OR = 0.80, 95% CI: 0.69-0.93, p = 0.003). Compared with the AA genotype, the GG genotype was significantly correlated with lower expression of both SNORD105 and PPAN (p < 0.01). Furthermore, the overexpressed SNORD105 up-regulated PPAN expression level (p < 0.05). Finally, the in vivo experiment showed that the overexpressed SNORD105 increased cell viability and motility in both HepG2 and Huh7 cell lines (p < 0.05).

Conclusions: To sum up, our results suggested that rs2305789 decreased the risk of HCC by reducing the expression of both SNORD105 and PPAN, which reduced HCC cell viability and motility.

Keywords: PPAN; SNORD105; hepatocellular carcinoma; rs2305789.

MeSH terms

  • Adult
  • Asian People / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Case-Control Studies
  • Cell Movement / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • RNA, Small Nucleolar / genetics*

Substances

  • Nuclear Proteins
  • PPAN protein, human
  • RNA, Small Nucleolar
  • SNORD105B RNA, human