Upregulation of Long Non-Coding Rna Rab1a-2 Induces Fgf1 Expression Worsening Lung Cancer Prognosis

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  • 作者：Wu, D., Yang, B., Chen, J., Xiong, H., Li, Y., Pan, Z., Cao, Y., Chen, J., Li, T., Zhou, S., Ling, X., Wei, Y., Li, G., Zhou, Y., Qiu, F., Yang, L. & Lu, J.
  • 期刊：Cancer letters 438, 116-125 (2018)
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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, 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.

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