Core Laboratory, School of Medicine, Sichuan Provincial People's Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu 610072, China.
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Oxid Med Cell Longev. 2022 Mar 11;2022:2623599. doi: 10.1155/2022/2623599. eCollection 2022.
The current treatment options for glioblastoma (GBM) can result in median survival of 15-16 months only, suggesting the existence of therapy-resistant factors. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play an essential role in the development of various brain tumors, including GBM. This study aimed to identify therapy-resistant and therapy-sensitive GBM associated lncRNAs and their role in GBM. We conducted a genome-wide transcriptional survey to explore the lncRNA landscape in 195 GBM brain tissues. Cell proliferation was evaluated by CyQuant assay and Ki67 immunostaining. Expression of MAD2L1 and CCNB2 was analyzed by western blotting. We identified 51 lncRNAs aberrantly expressed in GBM specimens compared with either normal brain samples or epilepsy non-tumor brain samples. Among them, 27 lncRNAs were identified as therapy-resistant lncRNAs that remained dysregulated after both radiotherapy and chemoradiotherapy; while 21 lncRNAs were identified as therapy-sensitive lncRNAs whose expressions were reversed by both radiotherapy and chemoradiotherapy. We further investigated the potential functions of the therapy-resistant and therapy-sensitive lncRNAs and demonstrated their relevance to cell proliferation. We also found that the expressions of several lncRNAs, including SNHG1 and UBL7-AS1, were positively correlated with cell-cycle genes' expressions. Finally, we experimentally confirmed the function of a therapy-resistant lncRNA, SNHG1, and a therapy-sensitive lncRNA, UBL7-AS1, in promoting cell proliferation in GBM U138MG cells. Our results demonstrated that knockdown of SNHG1 and UBL7-AS1 showed an additive effect in reducing cell proliferation in U138MG cells.
目前胶质母细胞瘤（GBM）的治疗选择只能导致中位生存时间为 15-16 个月，这表明存在治疗抵抗因素。新出现的证据表明，长链非编码 RNA（lncRNA）在包括 GBM 在内的各种脑肿瘤的发展中起着至关重要的作用。本研究旨在鉴定治疗抵抗和治疗敏感的 GBM 相关 lncRNA 及其在 GBM 中的作用。我们进行了全基因组转录谱调查，以探索 195 例 GBM 脑组织中的 lncRNA 图谱。通过 CyQuant 测定法和 Ki67 免疫染色评估细胞增殖。通过 Western 印迹分析 MAD2L1 和 CCNB2 的表达。我们鉴定了 51 个在 GBM 标本中与正常脑组织或癫痫非肿瘤脑组织相比表达异常的 lncRNA。其中，27 个 lncRNA 被鉴定为治疗抵抗性 lncRNA，它们在放射治疗和放化疗后仍然失调；而 21 个 lncRNA 被鉴定为治疗敏感性 lncRNA，它们的表达在放射治疗和放化疗后被逆转。我们进一步研究了治疗抵抗性和治疗敏感性 lncRNA 的潜在功能，并证明它们与细胞增殖有关。我们还发现，几种 lncRNA 的表达，包括 SNHG1 和 UBL7-AS1，与细胞周期基因的表达呈正相关。最后，我们通过实验证实了治疗抵抗性 lncRNA SNHG1 和治疗敏感性 lncRNA UBL7-AS1 在促进 GBM U138MG 细胞增殖中的作用。我们的结果表明，SNHG1 和 UBL7-AS1 的敲低在降低 U138MG 细胞增殖方面表现出相加效应。
