Comprehensive bioinformatic analysis reveals oncogenic role of H2A.Z isoforms in cervical cancer progression

Document Type : Original Article


1 Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, Ciudad de México

2 Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, 39090, Gro, México

3 Division of Infectious Diseases, Stanford University School of Medicine, United States

4 Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan, 14080, Mexico City, Mexico


Objective(s): Cervical cancer ranks as the fourth most common neoplasia in women worldwide in which epigenetic alterations play an important role. Several studies have reported pro-oncogenic role of the histone variant H2A.Z in different types of cancer; however, the role of H2A.Z in cervical cancer remains poorly studied. This study aimed to determine the potential role of H2A.Z in cervical cancer through a bioinformatic approach.
Materials and Methods: H2A.Z expression was analyzed in The Human Protein Atlas, The Cancer Genome Atlas, and Gene Expression Omnibus datasets. The promoter regions of H2AZ1 and H2AZ2 genes were downloaded from Expasy, and the prediction of transcription factor binding motifs was performed using CONSITE, Alibaba, and ALGGEN. ChIP-seq and RNA-seq data from HeLa-S3 cells were downloaded from ENCODE. The discovery motif was investigated using MEME-ChIP. The functional annotation was examined in Enrich.
Results: The expression of H2A.Z is elevated in cervical cancer. Interestingly, DNA methylation, copy number, and transcription factors AP2α and ELK1 are involved in H2A.Z overexpression. Additionally, H2A.Z is enriched on promoter and enhancer regions of genes involved in pathways associated with cancer development. In these regions, H2A.Z enables the recruitment of transcription factors such as NRF1, NFYA, and RNA Pol II. Finally, H2A.Z allows the expression of genes associated with proliferation in patients with cervical cancer.
Conclusion: Our findings suggest that H2A.Z overexpression and its presence in promoters and enhancers could be regulating the transcription of genes involved in cervical carcinogenesis.


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