Comprehensive bioinformatic analysis reveals oncogenic role of H۲A.Z isoforms in cervical cancer progression

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 H۲A.Z in different types of cancer; however, the role of H۲A.Z in cervical cancer remains poorly studied. This study aimed to determine the potential role of H۲A.Z in cervical cancer through a bioinformatic approach.Materials and Methods: H۲A.Z expression was analyzed in The Human Protein Atlas, The Cancer Genome Atlas, and Gene Expression Omnibus datasets. The promoter regions of H۲AZ۱ and H۲AZ۲ 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-S۳ cells were downloaded from ENCODE. The discovery motif was investigated using MEME-ChIP. The functional annotation was examined in Enrich.Results: The expression of H۲A.Z is elevated in cervical cancer. Interestingly, DNA methylation, copy number, and transcription factors AP۲α and ELK۱ are involved in H۲A.Z overexpression. Additionally, H۲A.Z is enriched on promoter and enhancer regions of genes involved in pathways associated with cancer development. In these regions, H۲A.Z enables the recruitment of transcription factors such as NRF۱, NFYA, and RNA Pol II. Finally, H۲A.Z allows the expression of genes associated with proliferation in patients with cervical cancer.Conclusion: Our findings suggest that H۲A.Z overexpression and its presence in promoters and enhancers could be regulating the transcription of genes involved in cervical carcinogenesis.

Keywords:

Cervical Cancer , Enhancers , H۲A.Z , H۲A.Z isoforms , Promoters , Proliferation