Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Int J Oncol. 2019 May;54(5):1651-1664. doi: 10.3892/ijo.2019.4758. Epub 2019 Mar 19.
The cancer susceptibility candidate 9 (CASC9) gene has been reported to exert an oncogenic effect in several types of cancer. However, its role in lung squamous cell carcinoma (LUSC) is unknown. Therefore, the present study examined the expression of CASC9 in LUSC and non‑cancer tissues by reverse transcription‑quantitative polymerase chain reaction assays and by data mining of high‑throughput public databases, including The Cancer Genome Atlas, the Gene Expression Omnibus, ArrayExpress and the Cancer Cell Line Encyclopedia. In vitro experiments were conducted to investigate the effects of CASC9 on the viability and the proliferation of LUSC cells. Furthermore, consulting the alteration status of CASC9 in LUSC from cBioPortal, functional enrichment analysis of co‑expressed genes, prediction of potential transcription factors, and inspection of adjacent protein‑coding genes were conducted to explore the potential molecular mechanism of CASC9 in LUSC. The results revealed that CASC9 was overexpressed in LUSC tissue, and significantly associated with the malignant progression of LUSC. In vitro experiments demonstrated that CASC9 knockdown by RNA interference attenuated the viability and proliferation of LUSC cells. Multiple copies of CASC9 gene were detected in 4 of 179 available sequenced LUSC cases. A functional enrichment analysis of 200 co‑expressed genes indicated that these genes were significantly associated with terms, including 'cell‑cell junction organization', 'desmosome organization', 'epidermis development', 'Hippo signaling pathway', 'pathogenic Escherichia coli infection' and 'PID HIF1 TF pathway'. Three genes, Fos‑related antigen 2 (FOSL2), SWI/SNF complex subunit SMARCC2, and transcription factor COE1 (EBF1), were predicted by lncRNAMap to be associated with CASC9. Among these, the expression of FOSL2 and EBF1 was positively and negatively correlated with the expression of CASC9, respectively. Two adjacent protein‑coding genes, cysteine‑rich secretory protein LCCL domain‑containing 1 and hepatocyte nuclear factor 4‑γ, were also positively correlated with CASC9 expression. In conclusion, the present data suggest that CASC9 serves as an oncogene in LUSC and may be a promising target for alternative therapeutic options for patients with this condition.
癌症易感性候选基因 9（CASC9）已被报道在多种类型的癌症中发挥致癌作用。然而，其在肺鳞状细胞癌（LUSC）中的作用尚不清楚。因此，本研究通过逆转录定量聚合酶链反应（RT-qPCR）检测和对高通量公共数据库（包括癌症基因组图谱、基因表达综合数据库、ArrayExpress 和癌症细胞系百科全书）的数据分析，检测了 CASC9 在 LUSC 组织和非癌组织中的表达情况。进行体外实验以研究 CASC9 对 LUSC 细胞活力和增殖的影响。此外，通过 cBioPortal 咨询 LUSC 中 CASC9 的改变状态、共表达基因的功能富集分析、潜在转录因子的预测以及相邻蛋白编码基因的检测，探讨了 CASC9 在 LUSC 中的潜在分子机制。结果表明，CASC9 在 LUSC 组织中表达上调，且与 LUSC 的恶性进展显著相关。体外实验表明，通过 RNA 干扰下调 CASC9 表达可减弱 LUSC 细胞的活力和增殖。在 179 例可获得测序的 LUSC 病例中，有 4 例存在多个 CASC9 基因拷贝。对 200 个共表达基因的功能富集分析表明，这些基因与“细胞-细胞连接组织”、“桥粒组织”、“表皮发育”、“Hippo 信号通路”、“致病性大肠杆菌感染”和“PID HIF1 TF 通路”等术语显著相关。lncRNAMap 预测 Fos 相关抗原 2（FOSL2）、SWI/SNF 复合物亚基 SMARCC2 和转录因子 COE1（EBF1）三个基因与 CASC9 相关。其中，FOSL2 和 EBF1 的表达与 CASC9 的表达呈正相关和负相关，而两个相邻的蛋白编码基因富含半胱氨酸的分泌蛋白 LCCL 结构域蛋白 1 和肝细胞核因子 4-γ与 CASC9 的表达也呈正相关。综上所述，本研究数据表明 CASC9 是 LUSC 的致癌基因，可能是该疾病患者替代治疗方案的有希望的靶点。
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