miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD
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Tao Hu1,2,*, Ye-Fei Chang1,*, zhangang Xiao3,4,*, Rui Mao5,*, Jun Tong6,*, Bo Chen7,*, Guang-Cai Liu1, Ying Hong1, Hong-Lan Chen1, Shu-Yi Kong2, Yan-Mei Huang1, Yan-Bin Xiyang2, Hua Jin8
1Department of Laboratory Medicine, The Third People’s Hospital of Yunnan Province, Kunming 650011, Yunnan, PR China
2Institute of Neuroscience, Kunming Medical University, Chenggong District, Kunming 650500, Yunnan, PR China
3Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, PR China
4School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT. Hong Kong, PR China
5School of Stomatologya, Kunming Medicine University, Kunming 650500, Yunnan, PR China
6Physical Eduction Department, Kunming Medical University, Kunming 650500, Yunnan, PR China
7Experiment Center for Medical Science Research, Kunming Medical University, Chenggong District, Kunming 650500, Yunnan, PR China
8Department of Anesthesiology, The First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan, PR China
*These authors contributed equally to this work
Yan-Bin Xiyang, email: [email protected]
Hua Jin, email: [email protected]
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
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.
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