Zou Zhen Wei, Ma Charlie, Medoro Lorraine, Chen Lili, Wang Bin, Gupta Roohi, Liu Ting, Yang Xian Zi, Chen Tian Tian, Wang Ruo Zhen, Zhang Wen Jie, Li Pin Dong
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Radiation Oncology, Fox Chase Cancer Center, American Oncologic Hospital, Pennsylvania, PA 19111, USA.
Oncotarget. 2016 Sep 20;7(38):61741-61754. doi: 10.18632/oncotarget.11437.
Long noncoding RNAs play a vital role in diverse biological processes such as embryonic development, cell growth, and tumorigenesis. In this study, we report that LncRNA ANRIL, which encodes a 3834-nt RNA that contains 19 exons at the antisense orientation of the INK4B-ARF-INK4A gene cluster, generally up-regulated in nasopharyngeal carcinoma [1]. In a cohort of 88 NPC patients, ANRIL was highly expressed in advanced-stage cancer. Multivariate analyses revealed that ANRIL expression could serve as an independent predictor of overall survival (P = 0.027) and disease-free survival (P = 0.033). Further investigation showed that knockdown of ANRIL significantly repressed NPC cell proliferation and transformation. We also found that ANRIL could induce the percentage of side population cells (SP cells) in NPC. To meet the urgent needs of energy provision, ANRIL can also reprogram glucose metabolism via increasing glucose uptake for glycolysis, which was regulated by the mTOR signal pathway to affect the expression of essential genes in glycolysis. We concluded that ANRIL could promote NPC progression via increasing cell proliferation, reprograming cell glucose metabolism and inducing side-population stem-like cancer cells. Our results also suggested that ANRIL may serve as a novel diagnostic or prognostic biomarker and a candidate target for new therapies in NPC.
长链非编码RNA在多种生物学过程中发挥着至关重要的作用,如胚胎发育、细胞生长和肿瘤发生。在本研究中,我们报道了LncRNA ANRIL,它编码一种3834个核苷酸的RNA,在INK4B-ARF-INK4A基因簇的反义方向含有19个外显子,在鼻咽癌中通常上调[1]。在一组88例鼻咽癌患者中,ANRIL在晚期癌症中高表达。多变量分析显示,ANRIL表达可作为总生存期(P = 0.027)和无病生存期(P = 0.033)的独立预测指标。进一步研究表明,敲低ANRIL可显著抑制鼻咽癌细胞的增殖和转化。我们还发现,ANRIL可诱导鼻咽癌中侧群细胞(SP细胞)的比例增加。为满足能量供应的迫切需求,ANRIL还可通过增加糖酵解的葡萄糖摄取来重新编程葡萄糖代谢,这是由mTOR信号通路调节的,以影响糖酵解中关键基因的表达。我们得出结论,ANRIL可通过增加细胞增殖、重新编程细胞葡萄糖代谢和诱导侧群干细胞样癌细胞来促进鼻咽癌进展。我们的结果还表明,ANRIL可能作为一种新的诊断或预后生物标志物以及鼻咽癌新疗法的候选靶点。