School of Pharmacy, Yancheng Teachers' University, Yancheng, Jiangsu, China.
Department of General Surgery, Xuhui District Central Hospital, Shanghai, China.
DNA Cell Biol. 2022 Jun;41(6):600-605. doi: 10.1089/dna.2021.0910. Epub 2022 May 16.
Genetic variants in several long noncoding RNA genes have been implicated in the occurrence and development of colorectal cancer (CRC). In this study, we explored the association between gene rs2276941 polymorphism and the risk and clinical stage of CRC. A direct sequencing method was used to detect the rs2276941 polymorphism in 576 CRC patients and 864 healthy individuals. Real-time quantitative PCR technology was used to explore the expression of HAND2-AS1 and hsa-miR-1275 in colorectal tissues with different rs2276941 genotypes. Dual-luciferase reporter assay was used to assess the function of the rs2276941 polymorphism. We found that the rs2276941 polymorphism was associated with a decreased risk of CRC (TT vs. CC, OR = 0.38, 95% CI = 0.16-0.89, = 0.03; TT vs. [CC+CT], OR = 0.40, 95% CI = 0.17-0.94, = 0.03). Furthermore, a significant negative correlation was observed between the expression of HAND2-AS1 and hsa-miR-1275 in colorectal tissues with rs2276941 TT genotype. Functional experimental results showed that the rs2276941 T allele might promote the binding of HAND2-AS1 to hsa-miR-1275. The current study results suggested that gene rs2276941 polymorphism affecting the binding of hsa-miR-1275 was associated with CRC risk and might serve as a CRC susceptibility biomarker.
几个长非编码 RNA 基因的遗传变异与结直肠癌(CRC)的发生和发展有关。在这项研究中,我们探讨了基因 rs2276941 多态性与 CRC 风险和临床分期的关系。采用直接测序法检测 576 例 CRC 患者和 864 例健康个体 rs2276941 多态性。采用实时定量 PCR 技术检测不同 rs2276941 基因型结直肠组织中 HAND2-AS1 和 hsa-miR-1275 的表达。双荧光素酶报告基因实验评估 rs2276941 多态性的功能。我们发现 rs2276941 多态性与 CRC 风险降低相关(TT 与 CC,OR=0.38,95%CI=0.16-0.89,=0.03;TT 与 [CC+CT],OR=0.40,95%CI=0.17-0.94,=0.03)。此外,在 rs2276941 TT 基因型的结直肠组织中,HAND2-AS1 和 hsa-miR-1275 的表达呈显著负相关。功能实验结果表明,rs2276941 T 等位基因可能促进 HAND2-AS1 与 hsa-miR-1275 的结合。本研究结果表明,基因 rs2276941 多态性影响 hsa-miR-1275 的结合与 CRC 风险相关,可能作为 CRC 易感性的生物标志物。