Journal
ONCOTARGET
Volume 7, Issue 38, Pages 61741-61754Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11437
Keywords
nasopharyngeal; carcinoma; LncRNA/ANRIL; mTOR pathway; glucose metabolism
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Funding
- National Natural Sciences Foundation of China [81301976, 81200313, 81502697]
- Applied Basic Research of Science and Technology Projects of Wuhan [2014060101010046]
- Independent Innovation Research Foundation of Huazhong University of Science and Technology [01-08-530059]
- Union Hospital Key Laboratory Foundation of Biological Target Therapy [02.03.2013-80]
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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.
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