miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD.
miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD.
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miR-1通过靶向G6PD抑制高危乳头瘤病毒相关人宫颈癌的进展
DOI：
10.18632/oncotarget.13344
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发表时间：
2016-12-27
期刊：
影响因子：
--
通讯作者：
Jin H
中科院分区：
文献类型：
--
作者：
Hu T;Chang YF;Xiao Z;Mao R;Tong J;Chen B;Liu GC;Hong Y;Chen HL;Kong SY;Huang YM;Xiyang YB;Jin H
异位葡萄糖-6-磷酸脱氢酶(G6PD)的表达可能与高危人乳头瘤病毒(HR-HPV16和18)感染相关的宫颈癌的发生有关。在这里，我们证明了microRNA-1(miR-1)与AGO蛋白联合作用于HR-HPV感染的人宫颈癌细胞中的G6PD。MIR-1抑制含有G6PD 3‘-UTR种子区的报告结构的表达，并抑制内源性G6PD的表达。下调miR-1可增加宫颈癌细胞G6PD的表达。回归分析显示，在HR-HPV16/18感染的宫颈癌患者中，miR-1水平与临床病理特征呈负相关。MIR-1过表达抑制宫颈癌细胞增殖，促进细胞凋亡，抑制裸鼠移植瘤生长。相反，海绵介导的miR-1基因敲除显著提高了宫颈癌细胞的存活率，减少了细胞凋亡，并支持了肿瘤的生长。G6PD表达的恢复在体外和体内都部分逆转了miR-1过表达的影响。此外，G6PD siRNA和miR-1海绵共转染部分逆转了miR-1海绵诱导的细胞活性下降和肿瘤生长。这些结果表明，miR-1通过靶向G6PD抑制HR-HPV16/18感染的宫颈癌的发生和发展，可能是一种有前途的新的候选治疗方法。
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.