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Background: Cervical cancer is the third most common malignancy in women worldwide, and it remains a leading cause of cancer-related death for women in developing countries.Though high-risk human papilloma virus (HPV) infection is considered the greatest risk factor for cervical cancer, seeking the contributing factors associated with progression is still necessary to improve the survival or prognosis of cervical cancer patients.Previous reports indicate that human pregnane X receptor (PXR) regulates cell proliferation and carcinogenesis in female reproductive tissue.Our data showed that activated PXR signaling control cervical tumorigenicity in vitro and in nude mice xenografts models.However, the potential cervical function of PXR or PXR pathway contributes to high-risk HPV associated cervical carcinogenesis remains unclear.Objectives: To identify novel host factor that interacts with high-risk human papilloma virus E6/E7 fusion protein and the functional interaction between human papilloma virus fusion protein and PXR in cervical carcinogenesis.Methods: Transfection assay, luciferase assay were utilized to assess the relationship between high-risk HPV E6/E7 fusion protein and PXR.The functional relevance of high-risk HPV E6/E7 fusion protein-PXR interaction was investigated in cell cultures and cervical carcinoma samples.Results: We investigated the expression and biological function of PXR in high risk HPV infection associated cervical carcinogenesis.Quantitative reverse transcription-PCR, western blot and immunohistochemistry were utilized to assess the expression of PXR both in high-risk HPV (+) cervical carcinoma cell lines and human tissue specimens.The effects of PXR signaling were investigated in high risk HPV (+)cervical carcinoma cell lines and human tissue specimens.Functionally, in HPV (+)cervical cells, activation of human PXR by rifampicin, ectopic expression of constitutively activated human VP-PXR or high-risk HPV fusion protein deregulated cervical cell proliferation.Mechanism analysis showed that the interaction between high-risk HPV E6/E7 fusion protein-PXR signaling is related with the cell-cycle Conclusions: We revealed a novel function of high-risk HPV E6/E7 fusion protein-PXR signaling in cervical carcinogenesis.