LncRNA ANRIL is up-regulated in nasopharyngeal carcinoma and promotes the cancer progression via increasing proliferation, reprograming cell glucose metabolism and inducing side-population stem-like cancer cells

Abstract

// Zhen Wei Zou 1 , Charlie Ma 2 , Lorraine Medoro 2 , Lili Chen 2 , Bin Wang 2 , Roohi Gupta 2 , Ting Liu 3 , Xian Zi Yang 4 , Tian Tian Chen 4 , Ruo Zhen Wang 5 , Wen Jie Zhang 6 , Pin Dong Li 1 1 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China 2 Department of Radiation Oncology, Fox Chase Cancer Center, American Oncologic Hospital, Pennsylvania, PA 19111, USA 3 Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China 4 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China 5 Department of Radiation Oncology, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China 6 Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China Correspondence to: Pin Dong Li, email: PinDong.Li@fccc.edu , lpd8204@163.com Keywords: nasopharyngeal, carcinoma, LncRNA/ANRIL, mTOR pathway, glucose metabolism Received: May 10, 2016      Accepted: August 11, 2016      Published: August 20, 2016 ABSTRACT 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.