1. HPV E7-mediated NCAPH ectopic expression regulates the carcinogenesis of cervical carcinoma via PI3K/AKT/SGK pathway
- Author
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Xiujie Cui, Liang Liu, Jiaxiang Lin, Wei Pan, John D. Hayball, Ranran Zhang, Tamara H. Cooper, Ying Zou, Xiaowen Qiao, Meng Wang, Xiao Wang, Shule Zhang, Yabin Zhou, Wang, Meng, Qiao, Xiaowen, Cooper, Tamara, Pan, Wei, Liu, Liang, Hayball, John, Lin, Jiaxiang, Cui, Xiujie, Zhou, Yabin, Zhang, Shule, Zou, Ying, Zhang, Ranran, and Wang, Xiao
- Subjects
Cancer Research ,cervical cancer ,Carcinogenesis ,Papillomavirus E7 Proteins ,Uterine Cervical Neoplasms ,Cell Cycle Proteins ,medicine.disease_cause ,Ectopic Gene Expression ,Phosphatidylinositol 3-Kinases ,Cell Movement ,E2F1 ,Promoter Regions, Genetic ,Tumor Stem Cell Assay ,Cervical cancer ,lcsh:Cytology ,Nuclear Proteins ,Prognosis ,Gene Expression Regulation, Neoplastic ,Treatment Outcome ,Female ,Protein Binding ,Signal Transduction ,Adult ,Epithelial-Mesenchymal Transition ,Immunology ,Mice, Nude ,Biology ,Protein Serine-Threonine Kinases ,Models, Biological ,Article ,Immediate-Early Proteins ,Cellular and Molecular Neuroscience ,Medical research ,Cell Line, Tumor ,medicine ,Gene silencing ,Animals ,Humans ,Neoplasm Invasiveness ,lcsh:QH573-671 ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,gynecological tumors ,tumor size ,NCAPH-induced cell proliferation ,Cell Biology ,medicine.disease ,Condensin I complex ,Transcription Factor AP-1 ,Cancer cell ,Cancer research ,Ectopic expression ,Protein Multimerization ,Proto-Oncogene Proteins c-akt ,E2F1 Transcription Factor - Abstract
Cervical cancer is one of the most common gynecological tumors in the world, and human papillomavirus (HPV) infection is its causative agent. However, the molecular mechanisms involved in the carcinogenesis of cervical cancer still require clarification. Here we found that knockdown of Non-SMC (Structural Maintenance of Chromosomes) condensin I complex subunit H (NCAPH) gene expression significantly inhibited the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of cervical cancer cells in vitro, and restrained xenograft tumor formation in vivo. Intriguingly, HPV E7 could form a positive feedback loop with NCAPH. E7 upregulated NCAPH gene expression via E2F1 which initiated NCAPH transcription by binding to its promoter directly. Silencing of NCAPH reduced E7 transcription via promoting the transition of AP-1 heterodimer from c-Fos/c-Jun to Fra-1/c-Jun. Moreover, the E7-mediated NCAPH overexpression was involved in the activation of the PI3K/AKT/SGK signaling pathway. In vivo, NCAPH expression in cervical cancer tissues was significantly higher than which in normal cervix and high-grade squamous intraepithelial lesion (HSIL) tissues, and its expression was significantly correlated with tumor size, depth of invasion and lymph node metastasis. Patients with high NCAPH expression had a significantly better survival outcomes than those with low-expression, suggesting that NCAPH-induced cell proliferation might sensitize cancer cells to adjuvant therapy. In conclusion, our results revealed the role of NCAPH in the carcinogenesis of cervical cancer in vitro and in vivo. The interaction between E7 and NCAPH expands the mechanism of HPV induced tumorigenesis and that of host genes regulating HPV E7.
- Published
- 2020