HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway via relieving miR-451 inhibitory effect on CAB39 in lung cancer cells.
HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway via relieving miR-451 inhibitory effect on CAB39 in lung cancer cells.
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HPV16 E6/E7 通过 PI3K/AKT 通路促进 GLUT1 的易位和葡萄糖摄取，从而缓解肺癌细胞中 miR-451 对 CAB39 的抑制作用。
DOI：
10.1177/2040622320957143
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发表时间：
2020
影响因子：
3.5
通讯作者：
Wu GP
中科院分区：
文献类型：
--
作者：
Wang HM;Lu YJ;He L;Gu NJ;Wang SY;Qiu XS;Wang EH;Wu GP
HPV 16 E6/E7蛋白是肺癌的主要致癌基因，只有长期持续感染才能导致肺癌。我们前期的研究表明HPV 16 E6/E7蛋白上调肺癌细胞中GLUT 1的表达。然而，E6和E7蛋白是否能促进GLUT 1的葡萄糖摄取及其分子机制尚不清楚。通过双向基因操作检测E6或E7、miR-451、CAB 39、PI 3 K/AKT和GLUT 1在肺癌细胞系中的调控关系。采用免疫荧光和流式细胞术检测CAB 39对GLUT 1向质膜转位的促进作用。流式细胞术和共聚焦显微镜检测GLUT 1的葡萄糖摄取水平。E6和E7蛋白的过表达显著下调了miR-451的表达水平，而miR-451的缺失进一步上调了其靶基因CAB 39在蛋白和mRNA水平的表达。随后，CAB 39在蛋白和mRNA水平上调GLUT 1的表达。我们的研究结果表明，HPV 16 E6/E7通过HPV-miR-451-CAB 39-GLUT 1轴上调GLUT 1的表达和激活。更有趣的是，我们发现CAB 39促进GLUT 1转运到质膜和葡萄糖摄取，并且这种促进依赖于PI 3 K/AKT通路。我们的发现为支持miR-451和CAB 39在HPV相关肺癌发病机制中的关键作用提供了新的证据。
HPV16 E6/E7 proteins are the main oncogenes and only long-term persistent infection causes lung cancer. Our previous studies have shown that HPV16 E6/E7 protein up-regulates the expression of GLUT1 in lung cancer cells. However, whether E6 and E7 protein can promote the glucose uptake of GLUT1 and its molecular mechanism are unclear. The regulatory relationships of E6 or E7, miR-451, CAB39, PI3K/AKT, and GLUT1 were detected by double directional genetic manipulations in lung cancer cell lines. Immunofluorescence and flow cytometry were used to detect the effect of CAB39 on promoting the translocation to the plasma membrane of GLUT1. Flow cytometry and confocal microscopy were performed to detect the glucose uptake levels of GLUT1. The overexpression both E6 and E7 proteins significantly down-regulated the expression level of miR-451, and the loss of miR-451 further up-regulated the expression of its target gene CAB39 at both protein and mRNA levels. Subsequently, CAB39 up-regulated the expression of GLUT1 at both protein and mRNA levels. Our results demonstrated that HPV16 E6/E7 up-regulated the expression and activation of GLUT1 through the HPV–miR-451–CAB39–GLUT1 axis. More interestingly, we found that CAB39 prompted GLUT1 translocation to the plasma membrane and glucose uptake, and this promotion depended on the PI3K/AKT pathway. Our findings provide new evidence to support the critical roles of miR-451 and CAB39 in the pathogenesis of HPV-related lung cancer.
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影响因子：
16
作者：
Lee, Eunice E.;Ma, Jing;Sacharidou, Anastasia;Mi, Wentao;Salato, Valerie K.;Nam Nguyen;Jiang, Youxing;Pascual, Juan M.;North, Paula E.;Shaul, Philip W.;Mettlen, Marcel;Wang, Richard C.
通讯作者：
Wang, Richard C.
影响因子：
3.7
作者：
Goto A;Tanaka M;Yoshida M;Umakoshi M;Nanjo H;Shiraishi K;Saito M;Kohno T;Kuriyama S;Konno H;Imai K;Saito H;Minamiya Y;Maeda D
通讯作者：
Maeda D
HPV 16 E6长期持续感染通过抑制肺癌细胞中的LKB1上调SP1和hTERT
影响因子：
3.7
作者：
Yang JH;Li XY;Wang X;Hou WJ;Qiu XS;Wang EH;Wu GP
通讯作者：
Wu GP
DOI：
10.26355/eurrev_201908_18657
发表时间：
2019-01-01
影响因子：
3.3
作者：
Liu, Y.;Li, H.;Sheng, Y. -L.
通讯作者：
Sheng, Y. -L.
影响因子：
--
作者：
Zhang W;Yin L;Song G;Han X;Yin Z;Luo D
通讯作者：
Luo D