CENPM upregulation by E5 oncoprotein of human papillomavirus promotes radiosensitivity in head and neck squamous cell carcinoma

Abstract

ObjectivesThis study aims to investigate how human papillomavirus (HPV) affects the key gene in the biological behaviors of head and neck squamous cell carcinoma (HNSCC) that leads to better response to radiotherapy. Materials and MethodsThe expression of key gene CENPM was analyzed using The Cancer Genome Atlas (TCGA) HNSCC data and HPV positive and HPV negative HNSCC tumors and cells. Assays with siRNAs, CRISPR/Cas9-based models, Western blot, qRT-PCR, ChIP, etc., were used to explore how HPV affects CENPM and response to radiotherapy for HNSCC. ResultsCENPM occupies the hub in the HPV-related gene network. HPV-positive HNSCC showed higher level of CENPM expression comparing with HPV-negative HNSCC. HPV E5 has the most pronounced impact on CENPM (R = 0.44, p = 0.00081). This might result from the binding of transcription factor E2F1 to CENPM. We further found that inhibition of CENPM expression in HPV-positive HNSCC cell line SCC47 increased resistance to X-ray radiation by approximately 59% under 2 Gy irradiation, which may be resulted from a reduced proportion of mitotic cells. ConclusionHPV E5 enhances CENPM expression by transcription factor E2F1 in HNSCC, which results in a radiosensitive profile in cell cycle redistribution of HNSCC. Thus, HPV infection in HNSCC provides profound evidence that underscores the magnitude of E2F1 control of CENPM expression illustrating the potential clinical benefit of CENPM examination for difficult-to-treat HPV-negative cancers.