Shen X-M, Han S, Liu N, Xu H-Q, Yan C-X, Yu C-J
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):1928-1935. doi: 10.26355/eurrev_202102_25091.
This study aims to explore the impact of LINC00887 on the malignant progression of glioma via upregulating CCND1.
LINC00887 and CCND1 levels in glioma patients in different tumor grades or metastasis statuses were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Kaplan-Meier curves were depicted for analyzing the prognostic potential of LINC00887 in glioma patients. Meanwhile, Pearson correlation test was conducted to assess the expression correlation between LINC00887 and CCND1 in glioma tissues. After knockdown of LINC00887 in LN229 and U251 cells, proliferative abilities were examined by cell counting kit-8 (CCK-8) and 5-Ethynyl-2'- deoxyuridine (EdU) assays. Subcellular distribution of LINC00887 was determined. Thereafter, RNA Binding Protein Immunoprecipitation (RIP) was performed to uncover the interaction between LINC00887 and CCND1. After α-amanitin induction in glioma cells overexpressing LINC00887, RNA degradation of CCND1 was examined at 0, 6, 12 and 24 h, respectively. Finally, the synergistic regulation of both LINC00887 and CCND1 on glioma proliferation was explored by CCK-8 assay.
It was found that LINC00887 was upregulated in glioma tissues, especially in stage III+IV or metastatic glioma cases. Overall survival was remarkably worse in glioma patients expressing a high level of LINC00887 than those with a low level. CCND1 was upregulated in glioma tissues as well, showing a positive correlation to LINC00887. In addition, LINC00887 was mainly distributed in the cytoplasm and interacted with CCND1, and it shortened the half-life of CCND1. Moreover, the knockdown of LINC00887 inhibited glioma cell proliferation, and this inhibitory effect was abolished by overexpression of CCND1.
LINC00887 is upregulated in glioma tissues, and it aggravates the malignant progression of glioma by upregulating CCND1.
本研究旨在探讨长链非编码RNA 00887（LINC00887）通过上调细胞周期蛋白D1（CCND1）对胶质瘤恶性进展的影响。
采用定量实时聚合酶链反应（qRT-PCR）检测不同肿瘤分级或转移状态的胶质瘤患者中LINC00887和CCND1的水平。绘制Kaplan-Meier曲线分析LINC00887在胶质瘤患者中的预后潜力。同时，进行Pearson相关性检验评估胶质瘤组织中LINC00887与CCND1的表达相关性。在LN229和U251细胞中敲低LINC00887后，通过细胞计数试剂盒-8（CCK-8）和5-乙炔基-2'-脱氧尿苷（EdU）检测法检测细胞增殖能力。确定LINC00887的亚细胞分布。此后，进行RNA结合蛋白免疫沉淀（RIP）实验以揭示LINC00887与CCND1之间的相互作用。在过表达LINC00887的胶质瘤细胞中用α-鹅膏蕈碱诱导后，分别在0、6、12和24小时检测CCND1的RNA降解情况。最后，通过CCK-8检测法探讨LINC00887和CCND1对胶质瘤增殖的协同调控作用。
发现LINC00887在胶质瘤组织中上调，尤其是在III + IV期或转移性胶质瘤病例中。LINC00887高表达的胶质瘤患者的总生存期明显低于低表达患者。CCND1在胶质瘤组织中也上调，与LINC00887呈正相关。此外，LINC00887主要分布在细胞质中并与CCND1相互作用，且缩短了CCND1的半衰期。而且，敲低LINC00887可抑制胶质瘤细胞增殖，而CCND1的过表达可消除这种抑制作用。
LINC00887在胶质瘤组织中上调，通过上调CCND1加重胶质瘤的恶性进展。
