AI Article Synopsis
- The study investigates how high-risk HPV E6 and E7 genes affect cellular homeostasis and their role in autophagy, a process important for maintaining cell health.
- In cervical cancer cell lines, downregulation of HPV 16E6/E7 was shown to inhibit autophagy, leading to reduced cell growth and increased early apoptosis.
- Results indicate that HPV 16E6/E7 activates autophagy through proteins Atg9B and LAMP1, suggesting that targeting this pathway could provide new therapeutic options for cervical cancer.
Article Abstract
Backgrounds: Although the role of high-risk human papillomavirus (HPV) E6 and E7 in cellular malignant transformation has been elucidated， the function of both genes in cellular homeostasis is still unknown. Autophagy functions in maintenance of cellular homeostasis play a key role in the initiation and development of cancer and infectious disease.
Methods: Cervical cancer cell lines SiHa and CaSki were utilized in this study.
Results: We found that HPV 16E6/E7 (16E6/E7) downregulation inhibited autophagy, and consequently suppressed cell proliferation and promoted early apoptosis. Transcriptome sequencing demonstrated that Atg9B and LAMP1 were downregulated in 16E6/E7 knockdown cells. Gene function experiments revealed that 16E6/E7 downregulation depressed Atg9B and LAMP1, and Atg9B and LAMP1 overexpression compensated, at least partially, autophagy blockage induced by 16E6/E7 knockdown. Immunoprecipitation assay showed that 16E7 interacted with Atg9B and dual-luciferase reporter system revealed that 16E6 most likely regulated -1750 to -2000 nt in Atg9B and -1800 to -2000 nt in LAMP1 promoter region.
Conclusions: Our findings verified that 16E6/E7 activated autophagy via accelerating autophagosome formation and degradation, and Atg9B and LAMP1 were involved in the process of 16E6/E7 modulating autophagy, suggesting that targeting autophagy may be a potential approach in cervical cancer therapeutics.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675746 | PMC |
| http://dx.doi.org/10.1002/cam4.2351 | DOI Listing |
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Article Synopsis
- The study investigates how high-risk HPV E6 and E7 genes affect cellular homeostasis and their role in autophagy, a process important for maintaining cell health.
- In cervical cancer cell lines, downregulation of HPV 16E6/E7 was shown to inhibit autophagy, leading to reduced cell growth and increased early apoptosis.
- Results indicate that HPV 16E6/E7 activates autophagy through proteins Atg9B and LAMP1, suggesting that targeting this pathway could provide new therapeutic options for cervical cancer.
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