Histone variant H2AZ1 drives lung cancer progression through the RELA-HIF1A-EGFR signaling pathway

Sep 21, 2026

Uploaded by Levi

Histone variants are increasingly linked to oncogenic tumor progression, yet the specific role and mechanism of histone variant H2AZ1 in lung cancer remain unclear. This study identifies H2AZ1 functions and molecular mechanisms by integrating RNA-seq and microarray analyses, tissue microarray immunohistochemistry, functional assays for proliferation and metastasis, and epigenomic and transcriptomic profiling including CUT&Tag-seq and ATAC-seq. Results show H2AZ1 is highly expressed and associated with poor survival, promoting malignant behaviors via RELA-HIF1A-EGFR signaling, indicating translational potential for precision therapy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Background

Histone variants and their relevance to cancer

Methods

Expression analysis and tissue validation

Functional assays

Epigenomic and molecular profiling

Results

H2AZ1 expression and patient survival association

Effects of H2AZ1 silencing

Mechanistic pathway through RELA-HIF1A-EGFR

Conclusion

Therapeutic targeting potential

Zhao et al. Cell Communication and Signaling (2024) 22:453 [https://doi.org/10.1186/s12964-024-01823-3](https://doi.org/10.1186/s12964-024-01823-3) Cell Communication and Signaling RESEARCH Open Access Histone variant H2AZ1 drives lung cancer progression through the RELA-HIF1A-EGFR signaling pathway Huijie Zhao 1,2, Xing Wu 1, Yinghan Wang 1, Xiuling Li2, Yuhui Du 1, Zhiqing Zhou 1, Yu Li 1, Yue Liu 1, Xiaofei Zeng 1,3 and Guoan Chen 1,4* Abstract Background A growing body of evidence indicates that histone variants play an oncogenic role in cancer progression. However, the role and mechanism of histone variant H2AZ1 in lung cancer remain poorly understood. In this study, we aim to identify novel functions and molecular mechanisms of H2AZ1 in lung cancer. Methods We analyzed H2AZ1 expression in lung adenocarcinoma using several RNA-seq and microarray datasets. Immunohistochemistry staining for H2AZ1 was performed on two sets of lung cancer tissue microarrays. To study the function of H2AZ1, we conducted assays for cell proliferation, colony formation, invasion, and migration. We employed CUT&Tag-seq, ATAC-seq, RNA-seq, and Western blotting to explore the regulatory patterns and potential mechanisms of H2AZ1 in lung adenocarcinoma. Results Our findings reveal that H2AZ1 is highly expressed in lung cancer and high levels of H2AZ1 mRNA are associated with poor patient survival. Silencing H2AZ1 impaired cell proliferation, colony formation, migration, and invasion. Mechanistically, our CUT&Tag-seq, ATAC-seq, and RNA-seq results showed that H2AZ1 is primarily deposited around TSS and affects multiple oncogenic signaling pathways. Importantly, we uncovered that H2AZ1 may drive lung cancer progression through the RELA-HIF1A-EGFR signaling pathway. Conclusion H2AZ1 plays an oncogenic role via several cancer-related pathways, including the RELA-HIF1A-EGFR axis in lung cancer. Intervention targeting H2AZ1 and its related signaling genes may have translational potential for precision therapy. Keywords Lung cancer, H2AZ1, RELA, HIF1A, EGFR *Correspondence: Guoan Chen [cheng@sustech.edu.cn](cheng@sustech.edu.cn) 1Department of Human Cell Biology and Genetics, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, No. 1088, Xueyuan Road, Nanshan District, Shenzhen, Guangdong Province 518055, China 2Department of Oncology, SunYat-sen Memorial Hospital, SunYat-sen University, Guangzhou, China 3National Key Laboratory for Tropical Crop Breeding, Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, Guangdong, China 4The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://](http://)[ ](http://)[creativecommons

FAQs

What is the primary focus of the study regarding H2AZ1?

The study aims to identify novel functions and molecular mechanisms of histone variant H2AZ1 in lung cancer progression.

Which experimental data were used to characterize H2AZ1 in lung adenocarcinoma?

The researchers analyzed H2AZ1 expression using RNA-seq and microarray datasets, validated it with immunohistochemistry on lung cancer tissue microarrays, and used CUT&Tag-seq, ATAC-seq, RNA-seq, and Western blotting to explore regulatory patterns and mechanisms.

How does H2AZ1 contribute to lung cancer progression according to the findings?

H2AZ1 is highly expressed in lung cancer and promotes malignant phenotypes; mechanistically, it is associated with deposition around TSS and may drive progression through the RELA-HIF1A-EGFR signaling pathway.

Sep 21, 2026

Uploaded by Levi