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

降低 SNORD105 和 PPAN 表达的 SNP 可降低中国人群罹患肝细胞癌的风险

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作者:Xuekun Chen, Qing Zhang, Zhenzhen Yang, Huan Yu, Yiling Qu, Rui Tan, Yuzhen Gao, Yan He, Lijuan Li

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.

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.

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.

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