miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD

// Tao Hu 1, 2, * , Ye-Fei Chang 1, * , zhangang Xiao 3, 4, * , Rui Mao 5, * , Jun Tong 6, * , Bo Chen 7, * , Guang-Cai Liu 1 , Ying Hong 1 , Hong-Lan Chen 1 , Shu-Yi Kong 2 , Yan-Mei Huang 1 , Yan-Bin Xiyang 2 , Hua Jin 8 1 Department of Laboratory Medicine, The Third People’s Hospital of Yunnan Province, Kunming 650011, Yunnan, PR China 2 Institute of Neuroscience, Kunming Medical University, Chenggong District, Kunming 650500, Yunnan, PR China 3 Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, PR China 4 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT. Hong Kong, PR China 5 School of Stomatologya, Kunming Medicine University, Kunming 650500, Yunnan, PR China 6 Physical Eduction Department, Kunming Medical University, Kunming 650500, Yunnan, PR China 7 Experiment Center for Medical Science Research, Kunming Medical University, Chenggong District, Kunming 650500, Yunnan, PR China 8 Department of Anesthesiology, The First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan, PR China * These authors contributed equally to this work Correspondence to: Yan-Bin Xiyang, email: xiyang_neuro@126.com Hua Jin, email: jinhuakm@163.com Keywords: glucose-6-phosphate dehydrogenase, miR-1, cervical cancer, high-risk human papillomaviruses, carcinogenic events Received: August 29, 2016      Accepted: November 08, 2016      Published: November 15, 2016 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.