Journal
CANCER LETTERS
Volume 438, Issue -, Pages 116-125Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.09.016
Keywords
Lung cancer; lncRNA; Lnc-RAB1A-2; FGF1; Survival
Categories
Funding
- National Natural Scientific Foundation of China [81473040, 81673267]
- Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program
- Science Foundation for Distinguished Young Scholars in Jiangsu [BK20160008]
- Guangdong Provincial Major Projects [2014KZDXM046]
- Guangdong Education Bureau Characteristic Innovation Project [2015KTSCX116]
- Guangzhou Science and Technology Program Pearl River Nova Projects [201710010049]
- [81402753]
- [81672303]
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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, over expression 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.
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