title: 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: 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.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Zhen Wei
authors.initials: ZW
authors.lastname: Zou
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, American Oncologic Hospital, Pennsylvania, PA 19111, USA.
authors.forename: Charlie
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, American Oncologic Hospital, Pennsylvania, PA 19111, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Medoro
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, American Oncologic Hospital, Pennsylvania, PA 19111, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, American Oncologic Hospital, Pennsylvania, PA 19111, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, American Oncologic Hospital, Pennsylvania, PA 19111, USA.
authors.forename: Roohi
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Xian Zi
authors.initials: XZ
authors.lastname: Yang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Tian Tian
authors.initials: TT
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
authors.forename: Ruo Zhen
authors.initials: RZ
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China.
authors.forename: Wen Jie
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Pin Dong
authors.initials: PD
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002277:Carcinoma / Q000378:metabolism*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D018572:Disease-Free Survival; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D008875:Middle Aged; D005810:Multigene Family; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000166:cytology; D016376:Oligonucleotides, Antisense; D062085:RNA, Long Noncoding / Q000235:genetics*; D058985:Side-Population Cells / Q000166:cytology*; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C561518:CDKN2B antisense RNA, human; D016376:Oligonucleotides, Antisense; D062085:RNA, Long Noncoding; D005947:Glucose
keywords: LncRNA/ANRIL; carcinoma; glucose metabolism; mTOR pathway; nasopharyngeal