Wang Yong, Gao Fulei, Lu Jian
Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
Nucleosides Nucleotides Nucleic Acids. 2025;44(7):531-541. doi: 10.1080/15257770.2024.2350513. Epub 2024 May 10.
Recently, a meta-analysis has shown that a potentially functional genetic polymorphism (rs7158663 A > G) on the cancer-associated lncRNA MEG3 is associated with the risk of many types of cancer. Given the important role of MEG3 in the development of hepatocellular carcinoma (HCC), the current study evaluated the association of the rs7158663 genetic polymorphism with HCC risk. A total of 271 HCC patients and 267 healthy individuals were included in the current case-control study. Direct sequencing was used to detect the rs7158663 locus genotype of the included individuals. The case-control study showed that the rs7158663 genetic polymorphism was associated with the increased risk of developing HCC [GA vs. GG: OR = 1.63, 95% CI = 1.14-2.34, = 0.009; AA vs. GG: OR = 2.10, 95% CI = 1.10-4.08, = 0.03; (GA + AA) vs. GG: OR = 1.70, 95% CI = 1.21-2.40, = 0.003; A vs. G: OR = 1.53, 95% CI = 1.17-2.00, = 0.002]. In addition, the genotype-tissue expression showed that the rs7158663 AA or GA genotype was associated with reduced MEG3 expression. Bioinformatic analysis showed that the rs7158663 genetic polymorphism not only affects the binding of transcription factors but also interacts with multiple genes through chromatin loops. In summary, the current findings suggest that the rs7158663 genetic polymorphism affecting MEG3 expression is associated with HCC risk and may serve as a marker of genetic susceptibility to HCC. However, the specific molecular mechanisms of the rs7158663 genetic polymorphism in the development of HCC need to be further revealed.
最近，一项荟萃分析表明，癌症相关长链非编码RNA MEG3上一个潜在的功能性基因多态性（rs7158663 A > G）与多种癌症风险相关。鉴于MEG3在肝细胞癌（HCC）发生发展中的重要作用，本研究评估了rs7158663基因多态性与HCC风险的相关性。本病例对照研究共纳入271例HCC患者和267名健康个体。采用直接测序法检测纳入个体的rs7158663位点基因型。病例对照研究表明，rs7158663基因多态性与HCC发生风险增加相关[GA与GG比较：OR = 1.63，95%CI = 1.14 - 2.34，P = 0.009；AA与GG比较：OR = 2.10，95%CI = 1.10 - 4.08，P = 0.03；（GA + AA）与GG比较：OR = 1.70，95%CI = 1.21 - 2.40，P = 0.003；A与G比较：OR = 1.53，95%CI = 1.17 - 2.00，P = 0.002]。此外，基因型-组织表达显示，rs7158663 AA或GA基因型与MEG3表达降低相关。生物信息学分析表明，rs7158663基因多态性不仅影响转录因子的结合，还通过染色质环与多个基因相互作用。总之，目前的研究结果表明，影响MEG3表达的rs7158663基因多态性与HCC风险相关，可能作为HCC遗传易感性标志物。然而rs7158663基因多态性在HCC发生发展中的具体分子机制有待进一步揭示。
