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

• Main Authors: Chen, X. (Author), Gao, Y. (Author), He, Y. (Author), Li, L. (Author), Qu, Y. (Author), Tan, R. (Author), Yang, Z. (Author), Yu, H. (Author), Zhang, Q. (Author)
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2021
• Subjects: adult; Adult; Article; Asian; Asians; cancer risk; cancer susceptibility; Carcinoma, Hepatocellular; case control study; Case-Control Studies; cell motility; cell motion; Cell Movement; cell viability; Chinese; controlled study; correlation analysis; female; Female; gene expression; gene expression regulation; Gene Expression Regulation, Neoplastic; gene overexpression; genetic association; Genetic Association Studies; genetic association study; genetic predisposition; Genetic Predisposition to Disease; genetics; genotype phenotype correlation; hepatocellular carcinoma; Hep-G2 cell line; Huh-7 cell line; human; Humans; in vivo study; liver cell carcinoma; Liver Neoplasms; liver tumor; major clinical study; male; Male; middle aged; Middle Aged; nuclear protein; Nuclear Proteins; pathology; Peter Pan protein; Polymorphism, Single Nucleotide; PPAN; PPAN protein, human; protein expression; real time polymerase chain reaction; regulator protein; risk reduction; RNA; RNA extraction; RNA, Small Nucleolar; rs2305789; single nucleotide polymorphism; small nucleolar RNA; SNORD105; SNORD105B RNA, human; unclassified drug; upregulation
• Online Access: View Fulltext in Publisher

 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. © 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.