Salmerón-Bárcenas Eric G, Zacapala-Gómez Ana E, Lozano-Amado Daniela, Castro-Muñoz Leonardo J, Leyva-Vázquez Marco A, Manzo-Merino Joaquín, Ávila-López Pedro A
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.
Iran J Basic Med Sci. 2021 Nov;24(11):1470-1481. doi: 10.22038/IJBMS.2021.58287..
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.
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.
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.
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.
宫颈癌是全球女性中第四大常见肿瘤，表观遗传改变在其中起着重要作用。多项研究报道了组蛋白变体H2A.Z在不同类型癌症中的促癌作用；然而，H2A.Z在宫颈癌中的作用仍研究不足。本研究旨在通过生物信息学方法确定H2A.Z在宫颈癌中的潜在作用。
在人类蛋白质图谱、癌症基因组图谱和基因表达综合数据库中分析H2A.Z的表达。从Expasy下载H2AZ1和H2AZ2基因的启动子区域，并使用CONSITE、阿里巴巴和ALGGEN进行转录因子结合基序预测。从ENCODE下载HeLa-S3细胞的染色质免疫沉淀测序（ChIP-seq）和RNA测序（RNA-seq）数据。使用MEME-ChIP研究发现基序。在Enrich中检查功能注释。
宫颈癌中H2A.Z的表达升高。有趣的是，DNA甲基化、拷贝数以及转录因子AP2α和ELK1参与了H2A.Z的过表达。此外，H2A.Z在与癌症发展相关途径的基因的启动子和增强子区域富集。在这些区域，H2A.Z能够招募转录因子，如核呼吸因子1（NRF1）、核转录因子Y亚基A（NFYA）和RNA聚合酶II（RNA Pol II）。最后，H2A.Z使得宫颈癌患者中与增殖相关的基因得以表达。
我们的研究结果表明，H2A.Z的过表达及其在启动子和增强子中的存在可能调控参与宫颈癌发生的基因的转录。
