A promoter variant of lncRNA GAS5 is functionally associated with the development of osteosarcoma.

Background: Previous studies showed that genetic variant rs145204276 in the promoter region of GAS5 was associated with the development of human cancer including colorectal cancer and hepatocellular cancer. This study aimed to investigate the role of rs145204276 in the development of osteosarcoma (OS).

Methods: 132 OS patients and 1270 healthy controls were recruited for the genotyping analysis of rs145204276. Promoter methylation level of GAS5 was determined for all patients. The tumor tissues and the adjacent normal tissue were collected from 42 patients during surgery and the relative expression of GAS5 was then quantified by Real-time PCR. The Chi-square test was used to determine the difference of genotype and allele frequency between the patients and the controls. The gene expression and the percentage of methylation alleles were compared among different genotypes of rs145204276 with One-way ANOVA test.

Results: Compared with the controls, patients were found to have significantly lower rate of genotype del/del (7.6% vs. 8.7%, p = 0.024). The frequency of allele del was significantly lower in the patients than in the controls (23.5% vs. 30.1%, p = 0.021). Compared with than patients with genotype ins/ins, those with genotype del/del had remarkably higher expression of GAS5 (0.0033 ± 0.0019 vs. 0.0018 ± 0.0006, p < 0.001). Patients with genotype del/del were found to have obviously hypermethylation at the 7th CpG site as compared with those with genotype ins/ins (38.7% ± 21.1% vs. 20.5% ± 8.2%, p < 0.001).

Conclusions: The genetic variant rs145204276 is functionally associated with the susceptibility of OS, which can function as a protective factor in the incidence of OS possibly through the regulation of GAS5.