Abstract
BackgroundsAlthough 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.MethodsCervical cancer cell lines SiHa and CaSki were utilized in this study.ResultsWe 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.ConclusionsOur 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.
Highlights
Cervical cancer has significantly declined in developed countries due to popularized cancer screening, but it still ranks the third common women's cancer in the world and is the leading cause of cancer death in less developed countries.[1-3]
Our results suggest that Atg9B and LAMP1 overexpressions compensate, at least partially, the autophagic blockage induced by 16E6E7 knockdown in cervical cancer cells
It is of significance to explore new strategies, other than the current therapeutic methods, to improve the outcome of patients with advanced cervical cancer
Summary
National Science Foundation of China, Grant/Award Number: 81572549; Molecular Typing and Precision Control of Cervical Cancer Based on Proteomics Feature, Grant/Award Number: 2016YFC0902900; National Key Research and Development Program: research on prevention and control of major chronic non‐infective disease, China, Grant/Award Number: 2016YFC1302900; Medical and Health science and technology project of Zhejiang Province, Grant/Award Number: 2017KY009; Gynecological Oncology Research Collaborative Network Construction, Grant/Award Number: 2015BA113B05
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