Cao Qiang, Li Pengchao, Cao Pu, Qian Jian, Du Mulong, Li Li, Wang Meilin, Qin Chao, Shao Pengfei, Zhang Zhengdong, Lu Qiang, Wang Zengjun
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Urology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China.
Front Oncol. 2020 May 20;10:785. doi: 10.3389/fonc.2020.00785. eCollection 2020.
The long non-coding RNA (lncRNA) H19 has been demonstrated to play a crucial role in carcinogenesis, including renal cell carcinoma (RCC). However, the impact of genetic variations in gene on RCC has not been investigated before. In the present study, we sought to evaluate whether genetic polymorphisms in are related to the susceptibility and mortality of RCC. We genotyped four widely studied polymorphisms in and assessed their relationship with susceptibility and prognosis of RCC in a case-control study compromising 1,027 cases and 1,094 controls. The functionality of the important polymorphism was further investigated by real-time polymerase chain reaction and luciferase reporter assay. We found that rs2839698 was significantly associated with risk and prognosis of RCC. Compared with the rs2839698 CC genotype, the variant genotypes (CT/TT) were significantly associated with increased risk of RCC ( = 0.023, OR = 1.21; 95% CI = 1.03-1.45). Besides, patients with variant genotypes (CT/TT) were more likely to develop large tumor ( = 0.003, OR = 1.47; 95% CI = 1.16-1.85) and advanced disease ( = 0.010, OR = 1.59; 95% CI = 1.12-2.26); and had a significantly unfavorable overall survival than those with the rs2839698 CC genotype (CT/TT vs. CC: Log-rank = 0.026, HR = 2.25, 95%CI = 1.07-4.75). Furthermore, the CT/TT genotypes were associated with significantly increased expression of in renal tissue. The luciferase reporter assays revealed the potential effect of rs2839698 variant on the binding of microRNAs to . Our results suggest that the rs2839698 variant may be a genetic predictor of susceptibility and mortality of RCC. The risk effects and the functional impact of the variant on still need further validation.
长链非编码RNA（lncRNA）H19已被证明在包括肾细胞癌（RCC）在内的肿瘤发生过程中起关键作用。然而，该基因的遗传变异对RCC的影响此前尚未得到研究。在本研究中，我们试图评估该基因的遗传多态性是否与RCC的易感性和死亡率相关。我们对该基因中四个广泛研究的多态性进行了基因分型，并在一项包含1027例病例和1094例对照的病例对照研究中评估了它们与RCC易感性和预后的关系。通过实时聚合酶链反应和荧光素酶报告基因检测进一步研究了重要多态性的功能。我们发现，rs2839698与RCC的风险和预后显著相关。与rs2839698 CC基因型相比，变异基因型（CT/TT）与RCC风险增加显著相关（P = 0.023，OR = 1.21；95%CI = 1.03 - 1.45）。此外，具有变异基因型（CT/TT）的患者更有可能发生大肿瘤（P = 0.003，OR = 1.47；95%CI = 1.16 - 1.85）和疾病进展（P = 0.010，OR = 1.59；95%CI = 1.12 - 2.26）；并且与rs2839698 CC基因型患者相比，总体生存率显著较差（CT/TT与CC：Log-rank P = 0.026，HR = 2.25，95%CI = 1.07 - 4.75）。此外，CT/TT基因型与肾组织中该基因的表达显著增加相关。荧光素酶报告基因检测揭示了rs2839698变异对微小RNA与该基因结合的潜在影响。我们的结果表明，rs2839698变异可能是RCC易感性和死亡率的遗传预测指标。该变异对该基因的风险效应和功能影响仍需进一步验证。
