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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.

SUBMITTER: Hu T 

PROVIDER: S-EPMC5349900 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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

Hu Tao T   Chang Ye-Fei YF   Xiao Zhangang Z   Mao Rui R   Tong Jun J   Chen Bo B   Liu Guang-Cai GC   Hong Ying Y   Chen Hong-Lan HL   Kong Shu-Yi SY   Huang Yan-Mei YM   Xiyang Yan-Bin YB   Jin Hua H  

Oncotarget 20161201 52


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 increas  ...[more]

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