HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway relieving miR-451 inhibitory effect on CAB39 in lung cancer cells
Background: 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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2020-09-01
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| Series: | Therapeutic Advances in Chronic Disease |
| Online Access: | https://doi.org/10.1177/2040622320957143 |
| _version_ | 1819081257512861696 |
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| author | Hong-Miao Wang Ying-Jie Lu Ling He Na-Jin Gu Shi-Yu Wang Xue-Shan Qiu En-Hua Wang Guang-Ping Wu |
| author_facet | Hong-Miao Wang Ying-Jie Lu Ling He Na-Jin Gu Shi-Yu Wang Xue-Shan Qiu En-Hua Wang Guang-Ping Wu |
| author_sort | Hong-Miao Wang |
| collection | DOAJ |
| description | Background: 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. Methods: 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. Results: 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. Conclusion: Our findings provide new evidence to support the critical roles of miR-451 and CAB39 in the pathogenesis of HPV-related lung cancer. |
| first_indexed | 2024-12-21T19:57:54Z |
| format | Article |
| id | doaj.art-53b4effa75094f8387422b36bad99922 |
| institution | Directory Open Access Journal |
| issn | 2040-6231 |
| language | English |
| last_indexed | 2024-12-21T19:57:54Z |
| publishDate | 2020-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Chronic Disease |
| spelling | doaj.art-53b4effa75094f8387422b36bad999222022-12-21T18:52:03ZengSAGE PublishingTherapeutic Advances in Chronic Disease2040-62312020-09-011110.1177/2040622320957143HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway relieving miR-451 inhibitory effect on CAB39 in lung cancer cellsHong-Miao WangYing-Jie LuLing HeNa-Jin GuShi-Yu WangXue-Shan QiuEn-Hua WangGuang-Ping WuBackground: 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. Methods: 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. Results: 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. Conclusion: Our findings provide new evidence to support the critical roles of miR-451 and CAB39 in the pathogenesis of HPV-related lung cancer.https://doi.org/10.1177/2040622320957143 |
| spellingShingle | Hong-Miao Wang Ying-Jie Lu Ling He Na-Jin Gu Shi-Yu Wang Xue-Shan Qiu En-Hua Wang Guang-Ping Wu HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway relieving miR-451 inhibitory effect on CAB39 in lung cancer cells Therapeutic Advances in Chronic Disease |
| title | HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway relieving miR-451 inhibitory effect on CAB39 in lung cancer cells |
| title_full | HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway relieving miR-451 inhibitory effect on CAB39 in lung cancer cells |
| title_fullStr | HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway relieving miR-451 inhibitory effect on CAB39 in lung cancer cells |
| title_full_unstemmed | HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway relieving miR-451 inhibitory effect on CAB39 in lung cancer cells |
| title_short | HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway relieving miR-451 inhibitory effect on CAB39 in lung cancer cells |
| title_sort | hpv16 e6 e7 promote the translocation and glucose uptake of glut1 by pi3k akt pathway relieving mir 451 inhibitory effect on cab39 in lung cancer cells |
| url | https://doi.org/10.1177/2040622320957143 |
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