title: miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD.
abstract: Ectopic glucose-6-phosphate dehydrogenase (G6PD) expression may contribute to tumorigenesis in cervical cancer associated with high-risk human papillomavirus (HR-HPV 16 and 18) infections. Here, we demonstrate that microRNA-1 (miR-1) in association with AGO proteins targets G6PD in HR-HPV-infected human cervical cancer cells. miR-1 inhibited expression of a reporter construct containing a putative G6PD 3'-UTR seed region and suppressed endogenous G6PD expression. Down-regulation of miR-1 increased G6PD expression in cervical cancer cells. Regression analysis revealed that miR-1 levels correlate negatively with the clinicopathologic features in HR-HPV 16/18-infected cervical cancer patients. miR-1 overexpression inhibited proliferation and promoted apoptosis in cervical cancer cells and reduced xenograft tumor growth in nude mice. Conversely, sponge-mediated miR-1 knockdown markedly increased viability and reduced apoptosis in cervical cancer cells and supported neoplasm growth. Restoration of G6PD expression partially reversed the effects of miR-1 overexpression both in vitro and in vivo. In addition, co-transfection of G6PD siRNA and miR-1 sponge partially reversed miR-1 sponge-induced reductions in cell viability and neoplasm growth. These results suggest that miR-1 suppresses the development and progression of HR-HPV 16/18-infected cervical cancer by targeting G6PD and may be a promising novel therapeutic candidate.
authors.affiliation: Department of Laboratory Medicine, The Third People's Hospital of Yunnan Province, Kunming 650011, Yunnan, PR China.|Institute of Neuroscience, Kunming Medical University, Chenggong District, Kunming 650500, Yunnan, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Laboratory Medicine, The Third People's Hospital of Yunnan Province, Kunming 650011, Yunnan, PR China.
authors.forename: Ye-Fei
authors.initials: YF
authors.lastname: Chang
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, PR China.|School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT. Hong Kong, PR China.
authors.forename: Zhangang
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: School of Stomatologya, Kunming Medicine University, Kunming 650500, Yunnan, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Mao
authors.affiliation: Physical Eduction Department, Kunming Medical University, Kunming 650500, Yunnan, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tong
authors.affiliation: Experiment Center for Medical Science Research, Kunming Medical University, Chenggong District, Kunming 650500, Yunnan, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, The Third People's Hospital of Yunnan Province, Kunming 650011, Yunnan, PR China.
authors.forename: Guang-Cai
authors.initials: GC
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, The Third People's Hospital of Yunnan Province, Kunming 650011, Yunnan, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Laboratory Medicine, The Third People's Hospital of Yunnan Province, Kunming 650011, Yunnan, PR China.
authors.forename: Hong-Lan
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Institute of Neuroscience, Kunming Medical University, Chenggong District, Kunming 650500, Yunnan, PR China.
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Kong
authors.affiliation: Department of Laboratory Medicine, The Third People's Hospital of Yunnan Province, Kunming 650011, Yunnan, PR China.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Huang
authors.affiliation: Institute of Neuroscience, Kunming Medical University, Chenggong District, Kunming 650500, Yunnan, PR China.
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Xiyang
authors.affiliation: Department of Anesthesiology, The First People's Hospital of Yunnan Province, Kunming 650032, Yunnan, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D052161:Human papillomavirus 18 / Q000302:isolation & purification*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000502:physiology*; D012306:Risk; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology
chemical_list: C544547:MIRN1 microRNA, human; D035683:MicroRNAs; D005954:Glucosephosphate Dehydrogenase
keywords: carcinogenic events; cervical cancer; glucose-6-phosphate dehydrogenase; high-risk human papillomaviruses; miR-1