Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Cell Death Dis. 2019 Jan 17;10(2):41. doi: 10.1038/s41419-018-1280-8.
Recent studies showed that lncRNA CASC9 was upregulated and acted as an oncogene in a variety of tumors. However, the expression and biological functions of CASC9 in oral squamous cell carcinoma (OSCC) remain unknown. In this study, we found for the first time that CASC9 was remarkably upregulated in OSCC tissues and cell lines compared with paired noncancerous tissues and normal oral epithelial cells. Highly expressed CASC9 is strongly associated with tumor size, clinical stage, regional lymph node metastasis and overall survival time in OSCC patients. In vitro, CASC9 knockdown in OSCC cells SCC15 and CAL27 significantly promotes autophagy and apoptosis, while inhibiting proliferation. Moreover, the expression levels of p-AKT, p-mTOR, P62 and BCL-2 were significantly decreased, while the expression levels of BAX and the LC3BII/LC3BI ratio were increased in CASC9-knockdown SCC15 and CAL27 cells. After the addition of the AKT activator SC79 in CASC9-knockdown SCC15 and CAL27 cells, we found that the increased autophagy and apoptosis were remarkably rescued. Furthermore, the increased apoptosis was remarkably rescued in CASC9-knockdown OSCC cells treated with the autophagy inhibitor Autophinib. In addition, CASC9 depletion suppressed tumor growth in vivo. In conclusion, our findings demonstrate that lncRNA CASC9 promotes OSCC progression through enhancing cell proliferation and suppressing autophagy-mediated cell apoptosis via the AKT/mTOR pathway. CASC9 could potentially be used as a valuable biomarker for OSCC diagnosis and prognosis.
最近的研究表明，lncRNA CASC9 在多种肿瘤中上调并发挥癌基因作用。然而，CASC9 在口腔鳞状细胞癌（OSCC）中的表达和生物学功能尚不清楚。在本研究中，我们首次发现 CASC9 在 OSCC 组织和细胞系中明显上调，与配对的非癌组织和正常口腔上皮细胞相比。高表达的 CASC9 与 OSCC 患者的肿瘤大小、临床分期、区域淋巴结转移和总生存时间强烈相关。在体外，OSCC 细胞 SCC15 和 CAL27 中的 CASC9 敲低显著促进自噬和凋亡，同时抑制增殖。此外，CASC9 敲低 SCC15 和 CAL27 细胞中 p-AKT、p-mTOR、P62 和 BCL-2 的表达水平显著降低，而 BAX 和 LC3BII/LC3BI 比值的表达水平升高。在添加 AKT 激活剂 SC79 后，我们发现 CASC9 敲低 SCC15 和 CAL27 细胞中增加的自噬和凋亡得到显著挽救。此外，CASC9 敲低 OSCC 细胞中自噬抑制剂 Autophinib 处理后增加的凋亡得到显著挽救。此外，CASC9 耗竭抑制体内肿瘤生长。总之，我们的研究结果表明，lncRNA CASC9 通过增强 AKT/mTOR 通路促进细胞增殖并抑制自噬介导的细胞凋亡，从而促进 OSCC 进展。CASC9 可能可作为 OSCC 诊断和预后的有价值的生物标志物。
