Huang Bo, Liu Chuan, Wu Qiong, Zhang Jing, Min Qinghua, Sheng Tianle, Wang Xiaozhong, Zou Yeqing
Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, 330006, China.
Jiangxi Province Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, 330006, China.
Biochem Biophys Res Commun. 2017 Jan 22;482(4):828-834. doi: 10.1016/j.bbrc.2016.11.120. Epub 2016 Nov 23.
Recently, long non-coding RNAs (lncRNAs) have been shown to have critical regulatory roles in tumourigenesis. Increasing evidence has suggested that lncRNA NEAT1 has been implicated in various types of human cancer. However, the potential biological roles and regulatory mechanisms of NEAT1 in pancreatic cancer (PC) remains unclear. Here, we found that the expression level of NEAT1 was higher in PC tissues compared to the corresponding non-tumor tissues. Besides, our findings indicate that high NEAT1 expression level is closely correlated with tumor progression and poor survival in PC patients. Furthermore, we also found that knockdown of NEAT1 remarkably suppressed cell proliferation by inducing cell cycle arrest and apoptosis promotion in PC cells. Moreover, bioinformatics analysis and luciferase reporter assay revealed that NEAT1 directly bound to the miR-506-3p, which has been reported to act as a tumor suppressor in diverse cancers. Additionally, our results confirmed that the tumor-promoting effects of NEAT1 in PC cells is at least partly through negative modulation of miR-506-3p. Overall, our results suggested that NEAT1 functions as an oncogenic lncRNA in PC, which could be a novel diagnostic and therapeutic target for PC.
最近,长链非编码RNA(lncRNAs)已被证明在肿瘤发生中具有关键的调控作用。越来越多的证据表明,lncRNA NEAT1与多种类型的人类癌症有关。然而,NEAT1在胰腺癌(PC)中的潜在生物学作用和调控机制仍不清楚。在此,我们发现与相应的非肿瘤组织相比,PC组织中NEAT1的表达水平更高。此外,我们的研究结果表明,PC患者中NEAT1的高表达水平与肿瘤进展和较差的生存率密切相关。此外,我们还发现敲低NEAT1可通过诱导PC细胞的细胞周期停滞和促进细胞凋亡来显著抑制细胞增殖。此外,生物信息学分析和荧光素酶报告基因检测显示,NEAT1直接与miR-506-3p结合,据报道miR-506-3p在多种癌症中发挥肿瘤抑制作用。此外,我们的结果证实,NEAT1在PC细胞中的促肿瘤作用至少部分是通过对miR-506-3p的负调控实现的。总体而言,我们的结果表明,NEAT1在PC中作为一种致癌lncRNA发挥作用,这可能是PC的一个新的诊断和治疗靶点。