环状RNA的全基因组微阵列分析揭示了胶质瘤治疗的新型生物标志物及其对胶质瘤进展的促进作用。
Genome-Wide Microarray Analysis of circRNAs Revealed Novel Biomarkers for Glioma Treatment and Their Promoting Effect on Glioma Progression.
作者信息
Lyu Xiaojuan, Zhou Lin, Fan Fengjuan, Dong Zhen
机构信息
Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430024, People's Republic of China.
Department of Histoembryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
出版信息
Onco Targets Ther. 2020 Apr 1;13:2739-2745. doi: 10.2147/OTT.S241347. eCollection 2020.
PURPOSE
As a novel type of non-coding RNAs, circRNAs were found to play important roles in cancer progression. In this study, we aim to investigate genome-wide circRNAs expression and potential functions in glioma to find new therapeutic targets for glioma treatment.
PATIENTS AND METHODS
A total of 92 pairs of glioma tissue samples and adjacent control samples were enrolled in this study. Microarray and bioinformatics tools were used to identify circRNAs expression in glioma. Relative expression of RNAs was validated by qRT-PCR. Cell viability and migration were measured by Cell Counting Kit-8 and wound-healing assay in U251 and SHG-44 cells. The statistical correlation and overall survival were calculated by Mann-Whitney -test and Kaplan-Meier method.
RESULTS
A total of 90 differentially expressed circRNAs were identified in glioma tissues compared to control. These circRNAs were mainly back-spliced forms chr1, chr6 and chr12 with a variable number of exons. QRT-PCR showed hsa_circ_0013520 and hsa_circ_0004379 were highly expressed in glioma tissues and cell lines. High expression of hsa_circ_0013520 and hsa_circ_0004379 was significantly correlated with tumor size (-value < 0.001), Karnofsky Performance Status (KPS, -value: 0.008 and 0.006) and TNM stage (-value: 0.004 and 0.005). Moreover, patients with higher expression level of hsa_circ_0013520 and hsa_circ_0004379 had a poorer overall survival (-value: < 0.01). Besides, loss-of-function experiments revealed that inhibition of hsa_circ_0013520 and hsa_circ_0004379 suppresses proliferation and invasion of glioma cells.
CONCLUSION
The present study is the first to report that hsa_circ_0013520 and hsa_circ_0004379 were up-regulated in glioma tissues and cell lines, and their expression was positively correlated with poor clinical features of glioma patients, which may serve as novel biomarkers for glioma diagnosis and therapy.
目的
作为一种新型非编码RNA，环状RNA（circRNA）被发现参与肿瘤进展过程。本研究旨在探究胶质瘤中全基因组circRNA的表达情况及其潜在功能，以寻找胶质瘤治疗的新靶点。
患者与方法
本研究共纳入92对胶质瘤组织样本及相邻对照样本。采用基因芯片和生物信息学工具鉴定胶质瘤中circRNA的表达情况。通过qRT-PCR验证RNA的相对表达水平。采用细胞计数试剂盒-8（Cell Counting Kit-8）和划痕实验检测U251和SHG-44细胞的活力和迁移能力。采用Mann-Whitney检验和Kaplan-Meier法计算统计相关性和总生存期。
结果
与对照相比，胶质瘤组织中共鉴定出90种差异表达的circRNA。这些circRNA主要是1号、6号和12号染色体的反向剪接形式，外显子数量不等。qRT-PCR显示，hsa_circ_0013520和hsa_circ_0004379在胶质瘤组织和细胞系中高表达。hsa_circ_0013520和hsa_circ_0004379的高表达与肿瘤大小（P值<0.001）、卡氏评分（KPS，P值分别为0.008和0.006）及TNM分期（P值分别为0.004和0.005）显著相关。此外，hsa_circ_0013520和hsa_circ_0004379表达水平较高的患者总生存期较差（P值<0.01）。此外，功能缺失实验表明，抑制hsa_circ_0013520和hsa_circ_0004379可抑制胶质瘤细胞的增殖和侵袭。
结论
本研究首次报道hsa_circ_0013520和hsa_circ_0004379在胶质瘤组织和细胞系中上调，其表达与胶质瘤患者的不良临床特征呈正相关，有望成为胶质瘤诊断和治疗的新型生物标志物。
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