LncRNA CASC9高表达激活PI3K/AKT信号通路促进口腔鳞癌细胞增殖转移

Overexpression of lncRNA CASC9 in oral squamous cell carcinoma promotes cancer cell proliferation and migration via activating the PI3K/AKT signaling pathway

摘要:

目的：探索lncRNA CASC9在口腔鳞癌（oral squamous cell carcinoma，OSCC）中的表达、功能及机制。方法：用原位杂交检测101例口腔鳞癌组织中CASC9的表达并行临床相关性和生存分析；siRNA干扰口腔鳞癌SCC15细胞中CASC9；qPCR和Western blot检测SCC15中PI3K、AKT和p-AKT的mRNA和蛋白表达水平；CCK-8实验、流式细胞和Transwell分别检测细胞的增殖、迁移和侵袭。结果：CASC9在口腔鳞癌组织中的表达明显升高（P=0.000）；CASC9表达水平与肿瘤大小、颈淋巴结转移及临床分期呈显著正相关（P<0.05），CASC9高表达的患者生存时间明显缩短（P=0.007）；CASC9是OSCC的独立危险因素（P<0.05）；沉默CASC9后，PI3K和p-AKT表达明显降低（P<0.05），SCC15细胞增殖、迁移和侵袭能力明显减弱（P<0.05）。结论：CASC9通过激活PI3K/AKT通路促进OSCC发展；CASC9可能是OSCC新的临床预后标志物和治疗靶点。

Abstract:

Objective：To explore the expression and function of long non-coding RNA（lncRNA） CASC9 in oral squamous cell carci－noma（OSCC），and to elucidate its potential mechanisms. Methods：The expression of CASC9 in OSCC tissues from 101 patients was determined by in situ hybridization assay，and the correlation between the expression of CASC9 and clinicopathological characteristics and survival were analyzed. CASC9 siRNA was transfected into the target OSCC cell line SCC15. The mRNA and protein expression levels of PI3K，AKT，and p-AKT in SCC15 cells were measured using qPCR and Western blot，and the proliferation，migration，and invasion of SCC15 cells were evaluated by CCK8 assay，flow cytometry，and Transwell assay，respectively. Results：The expression of CASC9 was significantly increased in OSCC tissues（P=0.000），and it was significantly positively correlated with tumor size，cervical lymph node metastasis，and clinical stage（P<0.05）. The overall survival was significantly shortened in OSCC patients with high expres－sion of CASC9（P=0.007）. CASC9 was an independent risk factor for OSCC（P<0.05）. After silencing of CASC9，the expression of PI3K and p-AKT was significantly reduced（P<0.05），and the proliferation，migration，and invasion of SCC15 cells were significantly attenuated（P<0.05）. Conclusion：CASC9 promotes OSCC progression by activating the PI3K/AKT pathway. CASC9 could potentially be a novel clinical prognostic marker and therapeutic target for OSCC.