lncRNA-HIT通过与E2F1相关促进非小细胞肺癌细胞增殖
lncRNA-HIT promotes cell proliferation of non-small cell lung cancer by association with E2F1
原文发布日期:2017-04-21
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Lung cancer is the leading cause of cancer-related death around the world. Long noncoding RNA (lncRNA) has pivotal roles in cancer occurrence and development. However, only a few lncRNAs have been functionally characterized. In the present study, we investigated the effects of lncRNA-HIT (HOXA transcript induced by TGFβ) expression on non-small cell lung cancer (NSCLC) cell phenotype with the gain-of-function and loss-of-function assays. We found that ectopic expression or knockdown of lncRNA-HIT markedly increased or decreased NSCLC cell proliferation, respectively. Moreover, we also showed that lncRNA-HIT interacted with E2F1 to regulate its target genes, such as Survivin, FOXM1, SKP2, NELL2 and DOK1. Collectively, our findings indicated that lncRNA-HIT affected the proliferation of NSCLC cells at least in part via regulating the occupancy of E2F1 in the promoter regions of its target genes. The lncRNA-HIT–E2F1 complex may be a potential target for NSCLC treatment.
肺癌是全球癌症相关死亡的主要原因。长链非编码RNA(lncRNA)在癌症发生发展中起关键作用,但目前仅有少数lncRNA的功能得到明确阐释。本研究通过功能获得性和功能缺失性实验,探讨了lncRNA-HIT(TGFβ诱导的HOXA转录本)表达对非小细胞肺癌(NSCLC)细胞表型的影响。我们发现lncRNA-HIT的异位表达或敲除分别显著促进或抑制NSCLC细胞增殖。更重要的是,我们还证实lncRNA-HIT通过与E2F1相互作用调控其靶基因(如Survivin、FOXM1、SKP2、NELL2和DOK1)的表达。总体而言,我们的研究结果表明lncRNA-HIT至少部分通过调控E2F1在其靶基因启动子区域的占据来影响NSCLC细胞增殖。lncRNA-HIT–E2F1复合物可能成为NSCLC治疗的潜在靶点。
lncRNA-HIT promotes cell proliferation of non-small cell lung cancer by association with E2F1
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