School of Life Sciences, Zhengzhou University, Zhengzhou, China.
Department of Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Cell Biochem Funct. 2020 Aug;38(6):733-742. doi: 10.1002/cbf.3540. Epub 2020 Apr 13.
Previous studies have shown that cancer susceptibility candidate 5 (CASC5) plays important roles in several types of cancer. But its expression and clinical significance in human pan-cancer remain largely unclear. In the present study, we comprehensively analysed the expression profile and prognostic values of CASC5 in pan-cancer across 33 cancer types based on the online TCGA analysis databases. CASC5 was found to be abnormally expressed in 16 types of cancer. In addition, dysregulated expression of CASC5 was closely associated with patient overall survival (OS) in kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD) and thymoma (THYM). By comparative analysis, we found that CASC5 was significantly up-regulated in LUAD and predicted poor patient OS. High CASC5 expression was closely correlated with tumour advanced stages of patients with LUAD. Through GSEA based on the KEGG database, CASC5 was found to be closely related to DNA replication and microRNA regulation in LUAD. Functionally, knockdown of CASC5 could inhibit cell proliferation of LUAD cells in vitro, rather than affecting cell migration and invasion. Mechanistically, CASC5 promoted proliferation of LUAD cells by targeting miR-139-5p. Collectively, our findings reveal that CASC5 is a novel oncogenic gene in LUAD and may be a potential clinical target and (or) biomarker for this human malignancy. SIGNIFICANCE OF THE STUDY: In this study, we for the first time comprehensively analysed the transcriptional level and prognostic significance of CASC5 in human pan-cancer across 33 cancer types using online TCGA databases. Our study indicates that CASC5 is aberrantly expressed in many tumours and is closely related to the patient overall survival of several tumour types. Our findings reveal that CASC5 is a novel oncogene in LUAD based on bioinformatic analysis and functional experiments. Mechanistically, CASC5 promoted LUAD proliferation by targeting miR-139-5p. Results of this study suggest that CASC5 is a potential clinical target and (or) biomarker for LUAD.
先前的研究表明,癌症易感性候选基因 5(CASC5)在多种类型的癌症中发挥着重要作用。但是,其在人类泛癌中的表达和临床意义在很大程度上尚不清楚。在本研究中,我们基于在线 TCGA 分析数据库,全面分析了 CASC5 在 33 种癌症类型中的泛癌表达谱和预后价值。研究发现,CASC5 在 16 种癌症中异常表达。此外,CASC5 的失调表达与肾透明细胞癌(KIRP)、肺腺癌(LUAD)、胰腺腺癌(PAAD)和胸腺瘤(THYM)患者的总生存(OS)密切相关。通过比较分析,我们发现 CASC5 在 LUAD 中显著上调,并预测患者 OS 不良。CASC5 高表达与 LUAD 患者肿瘤晚期密切相关。通过基于 KEGG 数据库的 GSEA 分析,发现 CASC5 与 LUAD 中的 DNA 复制和 microRNA 调节密切相关。功能上,CASC5 的敲低可抑制 LUAD 细胞的体外增殖,而不影响细胞迁移和侵袭。机制上,CASC5 通过靶向 miR-139-5p 促进 LUAD 细胞的增殖。综上所述,我们的研究结果表明,CASC5 是 LUAD 的一种新型致癌基因,可能是这种人类恶性肿瘤的潜在临床靶点和(或)生物标志物。研究意义:在本研究中,我们首次使用在线 TCGA 数据库全面分析了 CASC5 在 33 种癌症类型中的泛癌转录水平和预后意义。我们的研究表明,CASC5 在许多肿瘤中异常表达,与几种肿瘤类型的患者总生存密切相关。我们的研究结果表明,基于生物信息学分析和功能实验,CASC5 是 LUAD 的一种新型致癌基因。机制上,CASC5 通过靶向 miR-139-5p 促进 LUAD 细胞的增殖。本研究结果提示 CASC5 是 LUAD 的潜在临床靶点和(或)生物标志物。