State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China; Key Laboratory of Bio-Resource & Eco-Environment of MOE, College of Life Sciences, Sichuan University, Chengdu, 610065, China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
Cancer Lett. 2018 Apr 28;420:80-90. doi: 10.1016/j.canlet.2018.01.060. Epub 2018 Jan 31.
Long non-coding RNAs (lncRNAs) function as critical regulators to participate in tumor progression and metastasis. However, their roles in non-small cell lung cancer (NSCLC) are poorly understood. In this study, we found that the expression of the lncRNA linc00460 is significantly upregulated in NSCLC tumors and associated with poor prognosis for NSCLC patients, implying that linc00460 is important for lung cancer development. The accurate transcription initiation and termination sites of linc00460 were then identified by rapid-amplification of cDNA ends (RACE) technologies, and the sequencing data demonstrated that linc00460, predominantly located in the cytoplasm of lung cancer cells, is a novel transcript variant. Functional studies through gain- and loss-of-function strategies showed that linc00460 promotes cell migration and invasion through inducing epithelial-mesenchymal transition in lung cancer cells, whereas it has no effect on cell proliferation. The mechanism investigations through RNA pull-down assay and mass spectrometry identified that hnRNP K physically interacts with linc00460, and it also participates in cell migration and invasion. Therefore, our findings suggest that linc00460 acts as an oncogene in NSCLC to promote cell migration and highlight the potential prognostic and therapeutic values of linc00460 for NSCLC patients.
长链非编码 RNA（lncRNA）作为关键调节因子参与肿瘤的发生和转移。然而，它们在非小细胞肺癌（NSCLC）中的作用还知之甚少。在这项研究中，我们发现 lncRNA linc00460 在 NSCLC 肿瘤中的表达显著上调，并与 NSCLC 患者的不良预后相关，这表明 linc00460 对肺癌的发展很重要。然后通过快速扩增 cDNA 末端（RACE）技术鉴定 linc00460 的准确转录起始和终止位点，测序数据表明，linc00460 主要位于肺癌细胞的细胞质中，是一种新型转录变体。通过增益和缺失功能策略进行的功能研究表明，linc00460 通过诱导肺癌细胞上皮-间充质转化促进细胞迁移和侵袭，而对细胞增殖没有影响。通过 RNA 下拉测定和质谱分析的机制研究表明，hnRNP K 与 linc00460 发生物理相互作用，并参与细胞迁移和侵袭。因此，我们的研究结果表明，linc00460 在 NSCLC 中作为癌基因发挥作用，促进细胞迁移，并突出了 linc00460 对 NSCLC 患者的潜在预后和治疗价值。
