The State Key Lab of Respiratory Disease, The First Affiliated Hospital, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, 511436, China; Guangzhou Centre for Disease Control and Prevention, Guangzhou, 510440, China.
Department of Central Laboratory, The 5th Affiliated Hospital of Guanzhou Medical University, Guangzhou, 510700, China.
Cancer Lett. 2018 Dec 1;438:116-125. doi: 10.1016/j.canlet.2018.09.016. Epub 2018 Sep 12.
The chromosomal locations of lncRNAs (long non-coding RNAs, lncRNAs) infer their biological functions in cancer. Lnc-RAB1A-2, a Ras-related protein Rab-1A (RAB1A) upstream lncRNA, was chosen for assessment of its impact on lung cancer prognosis in a case-based analysis and investigation of its biological function though a series of functional assays. Lnc-RAB1A-2 was significantly upregulated in 276 lung cancer tissues compared with corresponding non-tumor tissues, and its expression level was significantly correlated with clinical stage and metastasis status in lung cancer patients. Patients with high expression levels of this lncRNA had a shorter median survival time (16.0 months vs. 23.0 months, P = 0.011 in southern samples; 8.0 months vs. 19.0 months, P = 0.020 in eastern samples; 13.0 months vs. 19.0 months, P = 0.002 in merged samples) and a higher risk of death than those with lower levels (HR = 1.52; 95% CI = 1.01-2.26, in merged samples). Additionally, overexpression of lnc-RAB1A-2 significantly promoted lung cancer cell proliferation in vitro and in vivo. Further analyses using digital gene expression tag profiling revealed that lnc-RAB1A-2 could affect the expression of fibroblast growth factor 1 (FGF1), a gene involved in the PI3K/AKT/mTOR pathway that is largely activated by RAB1A. FGF1 was confirmed to be a down-stream gene of lnc-RAB1A-2. Collectively, our study demonstrated that lnc-RAB1A-2 is associated with poor lung cancer prognosis by promoting lung cancer development.
lncRNAs（长非编码 RNA，lncRNAs）的染色体位置推断了它们在癌症中的生物学功能。lnc-RAB1A-2 是 Ras 相关蛋白 Rab-1A（RAB1A）的上游 lncRNA，我们选择它进行基于病例的分析，以评估其对肺癌预后的影响，并通过一系列功能测定来研究其生物学功能。与相应的非肿瘤组织相比，lnc-RAB1A-2 在 276 例肺癌组织中显著上调，其表达水平与肺癌患者的临床分期和转移状态显著相关。lncRNA 高表达的患者中位生存时间较短（南部样本中为 16.0 个月比 23.0 个月，P=0.011；东部样本中为 8.0 个月比 19.0 个月，P=0.020；合并样本中为 13.0 个月比 19.0 个月，P=0.002），死亡风险高于低表达水平的患者（HR=1.52；95%CI=1.01-2.26，合并样本）。此外，lnc-RAB1A-2 的过表达显著促进了肺癌细胞的体外和体内增殖。使用数字基因表达标签谱分析的进一步分析表明，lnc-RAB1A-2 可以影响成纤维细胞生长因子 1（FGF1）的表达，FGF1 是一个参与 PI3K/AKT/mTOR 通路的基因，该通路主要由 RAB1A 激活。FGF1 被确认为 lnc-RAB1A-2 的下游基因。总之，我们的研究表明，lnc-RAB1A-2 通过促进肺癌的发展与不良的肺癌预后相关。
