Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China.
Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, China.
Cancer Gene Ther. 2017 May;24(5):221-226. doi: 10.1038/cgt.2017.10. Epub 2017 Apr 21.
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）在癌症的发生和发展中起着关键作用。然而，只有少数 lncRNA 具有功能特征。在本研究中，我们通过功能获得和功能丧失实验研究了 lncRNA-HIT（TGFβ诱导的 HOXA 转录物）表达对非小细胞肺癌（NSCLC）细胞表型的影响。我们发现，lncRNA-HIT 的异位表达或敲低分别显著增加或降低了 NSCLC 细胞的增殖。此外，我们还表明，lncRNA-HIT 与 E2F1 相互作用，以调节其靶基因，如 Survivin、FOXM1、SKP2、NELL2 和 DOK1。总之，我们的研究结果表明，lncRNA-HIT 通过调节其靶基因启动子区域中 E2F1 的占据，至少部分地影响 NSCLC 细胞的增殖。lncRNA-HIT-E2F1 复合物可能是 NSCLC 治疗的潜在靶点。
