HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells
Background: There is an immediate need for research on the mechanism underlying telomerase activation and overexpression. Materials & Methods: A total of 174 patients with lung cancer ( n = 106) and benign lung disease ( n = 68) were recruited for the current study. The mRNA expression levels...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2020-05-01
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| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/1758835920917562 |
| _version_ | 1828390333483843584 |
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| author | Jing-Hua Yang Ming-Zhe Wu Xu-Bo Wang Shiyu Wang Xue-Shan Qiu En-Hua Wang Guang-Ping Wu |
| author_facet | Jing-Hua Yang Ming-Zhe Wu Xu-Bo Wang Shiyu Wang Xue-Shan Qiu En-Hua Wang Guang-Ping Wu |
| author_sort | Jing-Hua Yang |
| collection | DOAJ |
| description | Background: There is an immediate need for research on the mechanism underlying telomerase activation and overexpression. Materials & Methods: A total of 174 patients with lung cancer ( n = 106) and benign lung disease ( n = 68) were recruited for the current study. The mRNA expression levels of E6, E7, LKB1, Sp1, and hTERC in brushing cells were detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and hTERC amplification was also detected by fluorescence in situ hybridization (FISH). To investigate the potential mechanism, bidirectional genetic manipulation was performed in well-established lung cancer cell lines. Results: Our results indicated that the mRNA expression levels of E6, E7, Sp1, and hTERC and the amplification level of hTERC were significantly increased in the malignant group compared with those of the benign group ( p < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group ( p < 0.01). The correlation between E6, E7, Sp1, and hTERC expression was positive but was negative with LKB1 ( p < 0.01). Our results also showed that HPV16 E6/E7 downregulated the expression of LKB1 at both the protein and mRNA levels. The loss of LKB1 upregulated Sp1 expression, and also promoted Sp1 activity. Sp1 further upregulated hTERC at the mRNA and gene amplification levels. Thus, we proposed a HPV–LKB1–Sp1–hTERC axis of E6/E7 upregulation of hTERC expression. Conclusion: We demonstrated for the first time that E6 and E7 promoted hTERC mRNA expression and the amplification of hTERC by relieving the effect of LKB1 on the phosphorylation of Sp1. Sp1 further activated hTERC by directly binding to the promoter regions of hTERC. |
| first_indexed | 2024-12-10T06:42:39Z |
| format | Article |
| id | doaj.art-7edb8ff408534ca9917ef35b2b8a21a1 |
| institution | Directory Open Access Journal |
| issn | 1758-8359 |
| language | English |
| last_indexed | 2024-12-10T06:42:39Z |
| publishDate | 2020-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj.art-7edb8ff408534ca9917ef35b2b8a21a12022-12-22T01:58:44ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592020-05-011210.1177/1758835920917562HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cellsJing-Hua YangMing-Zhe WuXu-Bo WangShiyu WangXue-Shan QiuEn-Hua WangGuang-Ping WuBackground: There is an immediate need for research on the mechanism underlying telomerase activation and overexpression. Materials & Methods: A total of 174 patients with lung cancer ( n = 106) and benign lung disease ( n = 68) were recruited for the current study. The mRNA expression levels of E6, E7, LKB1, Sp1, and hTERC in brushing cells were detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and hTERC amplification was also detected by fluorescence in situ hybridization (FISH). To investigate the potential mechanism, bidirectional genetic manipulation was performed in well-established lung cancer cell lines. Results: Our results indicated that the mRNA expression levels of E6, E7, Sp1, and hTERC and the amplification level of hTERC were significantly increased in the malignant group compared with those of the benign group ( p < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group ( p < 0.01). The correlation between E6, E7, Sp1, and hTERC expression was positive but was negative with LKB1 ( p < 0.01). Our results also showed that HPV16 E6/E7 downregulated the expression of LKB1 at both the protein and mRNA levels. The loss of LKB1 upregulated Sp1 expression, and also promoted Sp1 activity. Sp1 further upregulated hTERC at the mRNA and gene amplification levels. Thus, we proposed a HPV–LKB1–Sp1–hTERC axis of E6/E7 upregulation of hTERC expression. Conclusion: We demonstrated for the first time that E6 and E7 promoted hTERC mRNA expression and the amplification of hTERC by relieving the effect of LKB1 on the phosphorylation of Sp1. Sp1 further activated hTERC by directly binding to the promoter regions of hTERC.https://doi.org/10.1177/1758835920917562 |
| spellingShingle | Jing-Hua Yang Ming-Zhe Wu Xu-Bo Wang Shiyu Wang Xue-Shan Qiu En-Hua Wang Guang-Ping Wu HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells Therapeutic Advances in Medical Oncology |
| title | HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells |
| title_full | HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells |
| title_fullStr | HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells |
| title_full_unstemmed | HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells |
| title_short | HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells |
| title_sort | hpv16 e6 e7 upregulate hterc mrna and gene amplification levels by relieving the effect of lkb1 on sp1 phosphorylation in lung cancer cells |
| url | https://doi.org/10.1177/1758835920917562 |
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