Upregulation of long noncoding RNA RAB11B-AS1 promotes tumor metastasis and predicts poor prognosis in lung cancer
Upregulation of long noncoding RNA RAB11B-AS1 promotes tumor metastasis and predicts poor prognosis in lung cancer
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DOI：
10.21037/atm.2020.04.52
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发表时间：
2020-05-01
影响因子：
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通讯作者：
Lu, Jiachun
中科院分区：
文献类型：
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作者：
Li, Tiegang;Wu, Di;Lu, Jiachun
背景：肺癌（LC）是中国和世界范围内癌症相关死亡的主要原因之一。尽管LC的诊断和治疗取得了进展，但LC的预后仍然很差。研究表明，长链非编码rna （long non-coding RNAs, lncRNAs）在癌变和癌症发展中起着至关重要的作用。方法：在体外和体内检测lnc-RAB11B-AS1在LC中的表达和潜在功能。本研究的所有实验均采用A549和PC-9细胞系，按照本文所述的方案进行。临床特征分析采用logistic回归、cox模型、log rank检验、qRT-PCR生化分析、转染、裸鼠模型，细胞生物学分析采用Transwell法、CCK-8法、流式细胞术、抢救实验、免疫组织化学。结果：LC组织中lnc-RAB11B-AS1较相应的非肿瘤组织明显过表达。lnc-RAB11B-AS1表达水平越高的患者总生存率越低。在功能上，lnc-RAB11B-AS1的过表达促进了LC细胞系的细胞增殖、迁移和侵袭能力，提示lnc-RAB11B-AS1可能在LC中起致瘤作用。lnc-RAB11B-AS1与RAB11B基因位于物理上的邻接位置，正调控RAR11B的表达，LC组织中RAB11B蛋白水平也与lnc-RAB11B-AS1表达水平呈正相关。RAB11B沉默部分消除了lnc-RAB11B- as1诱导的LC细胞系增殖。结论：本研究为lncrna驱动的癌变功能提供了新的证据。我们的研究结果强调了lnc-RAB11B-AS1和RAB11B在LC进展中的重要性，并表明lnc-RAB11B-ASI可能作为LC的一种新的有价值的预后生物标志物。
Background: Lung cancer (LC) is one of the leading causes of cancer-related mortality in China and worldwide. Despite the progress in diagnosis and treatment of LC, the prognosis of LC remains poor. Studies have demonstrated that long non-coding RNAs (lncRNAs) play a critical role in carcinogenesis and cancer development.Methods: Here we examined the expression and potential function of lnc-RAB11B-AS1 in LC both in vitro and in vivo. All experiments in this study were conducted using A549 and PC-9 cell lines according to protocols described in this paper. The clinic characteristics were analyzed using logistic regression, cox model, log rank test, biochemical analysis using qRT-PCR, transfections, nude mice model, and cell biological analysis using Transwell assay, CCK-8 assay, flow cytometry, and rescue experiments, and immunohistochemistry.Results: The results showed that lnc-RAB11B-AS1 was significantly overexpressed in LC tissues compared to the corresponding non-tumor tissues. Patients with a higher level of lnc-RAB11B-AS1 expression showed a poorer overall survival rate. Functionally, overexpression of lnc-RAB11B-AS1 promotes cell proliferation, migration and invasion abilities of LC cell lines, which suggests lnc-RAB11B-AS1 may play an oncogenic role in LC. lnc-RAB11B-AS1 was located in physical contiguity with RAB11B gene and found positively regulates the RAR11B expression, and the protein levels of RAB11B in LC tissues also found to positively correlated with the level of lnc-RAB11B-AS1 expression. RAB11B silencing partially abrogated lnc-RAB11B-AS1-induced proliferation of the LC cell lines used in this study.Conclusions: This study provided a novel evidence into the function of lncRNA-driven carcinogenesis. Our findings highlighted the importance of lnc-RAB11B-AS1 and RAB11B in LC progression and indicated that lnc-RAB11B-ASI may serve as a novel and valuable prognostic biomarker for LC.