Xu Wu, Che Dan-Dan, Chen Liang, Lv Sheng-Qing, Su Jun, Tan Jun, Liu Qing, Pan Ya-Wen
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Department of Neurosurgery, Affiliated Hospital of Jiujiang University, Jiujiang, 332000, Jiangxi, China.
J Mol Neurosci. 2021 Aug;71(8):1605-1613. doi: 10.1007/s12031-021-01793-y. Epub 2021 Feb 2.
Our previous study showed that the lncRNA UBE2R2-AS1 inhibits the growth and invasion of glioma cells and promotes apoptosis through the miR-877-3p/TLR4 pathway. In this study, it was further found that the expression of UBE2R2-AS1 in glioma tissues was decreased significantly, and gradually decreased with increasing clinical stage. Chi-square analysis showed that the expression of UBE2R2-AS1 was significantly correlated with the WHO stage of tumor and epilepsy. Using Kaplan-Meier univariate survival analysis, it was found that the expression of UBE2R2-AS1 correlated positively with the overall survival of patients with glioma, while multiple Cox regression analysis showed that the expression of UBE2R2-AS1 correlated positively with the overall survival of patients with glioma as a protective factor for glioma prognosis. The analysis of data from TCGA also showed that patients with high UBE2R2-AS1 levels or low miR-877-3p expression were more likely to have good survival outcomes. Further construction of a glioma xenograft model in nude mice showed that UBE2R2-AS1 overexpression inhibited the growth of tumors, and the inhibition of miR-877-3p expression had a similar effect. Simultaneous UBE2R2-AS1 overexpression and miR-877-3p inhibition further decreased the growth rate of tumors in nude mice. Taken together, the results of our study suggest that UBE2R2-AS1 is an important tumor suppressor gene in glioma, which may be a good marker and treatment target for the clinical detection of glioma.
我们之前的研究表明，长链非编码RNA UBE2R2-AS1通过miR-877-3p/TLR4途径抑制胶质瘤细胞的生长和侵袭，并促进细胞凋亡。在本研究中，进一步发现UBE2R2-AS1在胶质瘤组织中的表达显著降低，且随着临床分期的增加而逐渐降低。卡方分析表明，UBE2R2-AS1的表达与肿瘤的WHO分期及癫痫显著相关。采用Kaplan-Meier单因素生存分析发现，UBE2R2-AS1的表达与胶质瘤患者的总生存期呈正相关，而多因素Cox回归分析表明，UBE2R2-AS1的表达作为胶质瘤预后的保护因素与胶质瘤患者的总生存期呈正相关。对TCGA数据的分析还表明，UBE2R2-AS1水平高或miR-877-3p表达低的患者更有可能有良好的生存结果。进一步在裸鼠中构建胶质瘤异种移植模型表明，UBE2R2-AS1过表达抑制肿瘤生长，抑制miR-877-3p表达也有类似效果。同时过表达UBE2R2-AS1并抑制miR-877-3p可进一步降低裸鼠肿瘤的生长速度。综上所述，我们的研究结果表明，UBE2R2-AS1是胶质瘤中一个重要的肿瘤抑制基因，可能是胶质瘤临床检测的良好标志物和治疗靶点。
