Department of Radiotherapy (Ward II), Qinhuangdao First Hospital, No.258 Wenhua Road, Haigang District, Qinhuangdao, 066000, Hebei, People's Republic of China.
Biochem Genet. 2022 Aug;60(4):1159-1176. doi: 10.1007/s10528-021-10145-9. Epub 2021 Nov 19.
LncRNA-PTENP1 was reported to promote multiple myeloma cancer stem cell proliferation, and the G allele of rs7853346 polymorphism in lncRNA-PTENP1 was demonstrated to enhance the effect of lncRNA-PTENP1. In this study, we aimed to study the potential effect of lncRNA-PTENP1 and CCR2 mRNA polymorphisms on cognitive impairment in glioma patients. In this study, 279 glioma patients were recruited and grouped according to their genotypes of rs7853346 in PTENP1 and rs1799864 in CCR1. Pathogenic parameters were collected from patients before radiotherapy (month 0) or at month 1 and month 3 after radiotherapy to study the effect of rs7853346 and rs1799864 on cognitive impairment. Sequence analysis, luciferase assay, real-time PCR, and Western blot were performed to study the regulatory relationships between lncRNA-PTENP1, miR-18b, and CCR2. The glioma patient groups exhibited no significant differences concerning basic characteristics. However, the CG&GG/GG genotype alleviated radiotherapy-induced cognitive impairment by exhibiting the highest MMSE among the four groups. On the contrary, parameters including the severity of depression, bladder control, global health status, itchy skin, and weakness of legs all showed no difference among different patient groups at month 0, month 1, and month 3. Also, a long-term positive effect of CG&GG/GG genotype on role functioning and social functioning was also observed after radiotherapy. Compared with patients carrying the CC genotype of rs7853346, the expression of lncRNA-PTENP1 was reduced while the miR-19b level was elevated in patients carrying the CG&GG genotypes of rs7853346. Moreover, the expression of CCR2 mRNA was the highest in the CC/GA&AA group and the lowest in the CG&GG/GG group. Subsequent sequence analysis and luciferase assay indicated that miR-19b could bind to lncRNA-PTENP1 and 3'UTR of CCR2 mRNA, and the knockdown of lncRNA-PTENP1 led to evident up-regulation of miR-19b and down-regulation of CCR2 mRNA/protein in a cellular model, thus verifying the presence of the lncRNA-PTENP1/miR-19b/CCR2 mRNA signaling pathway. In conclusion, by studying the changes in the key parameters of glioma patients who were subjected to radiotherapy, we concluded that the rs7853346 polymorphism in lncRNA-PTENP1 and the rs1799864 polymorphism in CCR2 could independently affect cognitive impairment, while a more significant combined effect on cognitive impairment was exerted in glioma patients via the signaling pathway of PTENP1/miR-19b/CCR2.
LncRNA-PTENP1 被报道能促进多发性骨髓瘤肿瘤干细胞的增殖，lncRNA-PTENP1 中的 rs7853346 多态性的 G 等位基因被证明能增强 lncRNA-PTENP1 的作用。在这项研究中，我们旨在研究 lncRNA-PTENP1 和 CCR2 mRNA 多态性对胶质瘤患者认知障碍的潜在影响。在这项研究中，招募了 279 名胶质瘤患者，并根据他们在 PTENP1 中的 rs7853346 和 CCR1 中的 rs1799864 的基因型进行分组。在放疗前（第 0 个月）或放疗后第 1 个月和第 3 个月收集患者的病理参数，以研究 rs7853346 和 rs1799864 对认知障碍的影响。进行序列分析、荧光素酶测定、实时 PCR 和 Western blot，以研究 lncRNA-PTENP1、miR-18b 和 CCR2 之间的调控关系。胶质瘤患者组在基本特征方面无显著差异。然而，CG&GG/GG 基因型通过在四组中表现出最高的 MMSE 缓解了放疗引起的认知障碍。相反，在第 0 个月、第 1 个月和第 3 个月，不同患者组在抑郁严重程度、膀胱控制、总体健康状况、皮肤瘙痒和腿部无力等参数方面均无差异。此外，在放疗后，CG&GG/GG 基因型对角色功能和社会功能也有长期的积极影响。与携带 rs7853346 的 CC 基因型的患者相比，携带 rs7853346 的 CG&GG 基因型的患者中 lncRNA-PTENP1 的表达减少，而 miR-19b 的水平升高。此外，CCR2 mRNA 的表达在 CC/GA&AA 组最高，在 CG&GG/GG 组最低。随后的序列分析和荧光素酶测定表明，miR-19b 可以与 lncRNA-PTENP1 和 CCR2 mRNA 的 3'UTR 结合，在细胞模型中敲低 lncRNA-PTENP1 导致 miR-19b 的明显上调和 CCR2 mRNA/蛋白的下调，从而验证了 lncRNA-PTENP1/miR-19b/CCR2 mRNA 信号通路的存在。总之，通过研究接受放疗的胶质瘤患者关键参数的变化，我们得出结论，lncRNA-PTENP1 中的 rs7853346 多态性和 CCR2 中的 rs1799864 多态性可以独立影响认知障碍，而 lncRNA-PTENP1/miR-19b/CCR2 信号通路在胶质瘤患者中对认知障碍具有更显著的联合作用。
