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Differential Transcriptomic Profiles in Gastric Cell Lines Regulated by Histone H3 Isoform and Variants
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16
DOI: DOI: 10.1055/s-0044-1788232
*Corresponding author: (e-mail: sgupta@actrec.gov.in).
Abstract
Background: Earlier studies have shown H3.2 histone isoform associates with repressive histone marks and H3.3 with active PTMs. Therefore, an insight into regulation of gene expression by differential genomic occupancy of H3.2 and H3.3 will give an understanding of altered biological pathways in gastric cancer.
Materials and Methods: H3.2 and H3.3 levels and their PTMs were studied by western blotting in gastric cancer cell lines. The purified RNA was subjected to RNA-sequencing analysis for differential gene expression. Further, their levels and genomic occupancy at primary and metastatic tumor was studied in in vivo orthotopic gastric cancer model.
Results: The increase of H3.2 isoform with a decrease of H3.3 associates with alteration in H3K9me3 and H3K9ac in human gastric cancer cell lines. Moreover, H3.2 decreases with an increase of H3.3 in metastasis compared to the primary gastric cancer cell line. The alteration in the H3 proteins and specific modification are also observed in primary and metastatic tumors of in vivo orthotopic mice model. RNA-sequencing analysis has shown upregulation of metabolic pathways with downregulation of cell surface interaction pathways in gastric cancer cell lines. Moreover, the chromatin modifiers associated with global chromatin condensation were found to be upregulated in cancer cell lines.
Conclusion: Preliminary studies have shown changes in H3.2 and H3.3 associated with different cellular cancer phenotypes in primary and metastatic tumors. The global chromatin condensation, an increase in energy and metabolic pathways, and a decrease in cell–cell communication, potentially provide survival advantages and enhance the metastatic potential of gastric cancer cells.
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
*Corresponding author: (e-mail: sgupta@actrec.gov.in).
Abstract
Background: Earlier studies have shown H3.2 histone isoform associates with repressive histone marks and H3.3 with active PTMs. Therefore, an insight into regulation of gene expression by differential genomic occupancy of H3.2 and H3.3 will give an understanding of altered biological pathways in gastric cancer.
Materials and Methods: H3.2 and H3.3 levels and their PTMs were studied by western blotting in gastric cancer cell lines. The purified RNA was subjected to RNA-sequencing analysis for differential gene expression. Further, their levels and genomic occupancy at primary and metastatic tumor was studied in in vivo orthotopic gastric cancer model.
Results: The increase of H3.2 isoform with a decrease of H3.3 associates with alteration in H3K9me3 and H3K9ac in human gastric cancer cell lines. Moreover, H3.2 decreases with an increase of H3.3 in metastasis compared to the primary gastric cancer cell line. The alteration in the H3 proteins and specific modification are also observed in primary and metastatic tumors of in vivo orthotopic mice model. RNA-sequencing analysis has shown upregulation of metabolic pathways with downregulation of cell surface interaction pathways in gastric cancer cell lines. Moreover, the chromatin modifiers associated with global chromatin condensation were found to be upregulated in cancer cell lines.
Conclusion: Preliminary studies have shown changes in H3.2 and H3.3 associated with different cellular cancer phenotypes in primary and metastatic tumors. The global chromatin condensation, an increase in energy and metabolic pathways, and a decrease in cell–cell communication, potentially provide survival advantages and enhance the metastatic potential of gastric cancer cells.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India