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肺鳞状细胞癌中环状RNA表达的基因芯片表达谱分析及生物信息学分析

Microarray expression profiling and bioinformatics analysis of circular RNA expression in lung squamous cell carcinoma.

作者信息

Xu Jiali, Shu Yongqian, Xu Tongpeng, Zhu Wei, Qiu Tianzhu, Li Jun, Zhang Meiling, Xu Jing, Guo Renhua, Lu Kaihua, Zhu Lingjun, Yin Yongmei, Gu Yanhong, Liu Lianke, Liu Ping, Wang Rong

机构信息

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province HospitalNo. 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, People's Republic of China.

出版信息

Am J Transl Res. 2018 Mar 15;10(3):771-783. eCollection 2018.

Abstract

Circular RNAs (circRNAs) are novel noncoding RNAs with a wide range of physiological and pathological activities. However, the expression profile and roles in lung squamous cell carcinoma (LSCC) remain largely unknown. Therefore, we investigated the expression profile of circRNAs in three LSCC and matched adjacent normal tissues using microarray. Total 216 differentially expressed circRNAs were identified, including 135 upregulated and 81 downregulated ones in LSCC tissues. Bioinformatics analysis revealed that these differentially expressed circRNAs were potentially implicated in carcinogenesis using Gene ontology (GO) and KEGG pathway analyses. By constructing miRNA-circRNA interaction network, a total of ten key circRNAs, including 6 upregulated and 4 downregulated circRNAs were further screened and then confirmed using qRT-PCR analysis in another 40 paired of LSCC tissues and adjacent normal tissues. In addition, Kaplan-Meier survival analysis demonstrated that the overall survival time of LSCC patients with high hsa_circRNA_103827 expression and low hsa_circRNA_000122 was significantly shorter (<0.001). In conclusion, this study provides evidence that circRNAs are differentially expressed in LSCC and closely related to the carcinogenesis of LSCC. Among these, hsa_circRNA_103827 and hsa_circRNA_000122 might be served as potential prognostic biomarkers and therapeutic target for LSCC.

摘要

环状RNA(circRNAs)是一类具有广泛生理和病理活性的新型非编码RNA。然而,其在肺鳞状细胞癌(LSCC)中的表达谱及作用仍 largely未知。因此,我们使用微阵列技术研究了3例LSCC组织及配对的癌旁正常组织中circRNAs的表达谱。共鉴定出216个差异表达的circRNAs,其中LSCC组织中有135个上调,81个下调。生物信息学分析通过基因本体论(GO)和KEGG通路分析揭示,这些差异表达的circRNAs可能与致癌作用有关。通过构建miRNA-circRNA相互作用网络,进一步筛选出总共10个关键circRNAs,包括6个上调和4个下调的circRNAs,然后在另外40对LSCC组织和癌旁正常组织中使用qRT-PCR分析进行验证。此外,Kaplan-Meier生存分析表明,高表达hsa_circRNA_103827和低表达hsa_circRNA_000122的LSCC患者的总生存时间显著缩短(<0.001)。总之,本研究提供了证据表明circRNAs在LSCC中差异表达且与LSCC的致癌作用密切相关。其中,hsa_circRNA_103827和hsa_circRNA_000122可能作为LSCC潜在的预后生物标志物和治疗靶点。

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