KFU. Card publication. KNOCKOUT OF THE HISTONE METHYLTRANSFERASE NSD1 LEADS TO A DECREASE IN CELL PROLIFERATION AND AN INCREASE IN SENSITIVITY TO CISPLATIN IN LARYNGEAL SQUAMOUS CELL CARCINOMA

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KNOCKOUT OF THE HISTONE METHYLTRANSFERASE NSD1 LEADS TO A DECREASE IN CELL PROLIFERATION AND AN INCREASE IN SENSITIVITY TO CISPLATIN IN LARYNGEAL SQUAMOUS CELL CARCINOMA

Form of presentation

Articles in international journals and collections

Year of publication

2023

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Authors, employees of KFU

Abramova Zinaida Ivanovna, author

Bulatov Emil Rafaelevich, author

Bibliographic description in the original language

Topchu I.A, Tikhomirova M.V, Bulatov E.R, KNOCKOUT OF THE HISTONE METHYLTRANSFERASE NSD1 LEADS TO A DECREASE IN CELL PROLIFERATION AND AN INCREASE IN SENSITIVITY TO CISPLATIN IN LARYNGEAL SQUAMOUS CELL CARCINOMA//Siberian Journal of Oncology. - 2023. - Vol.22, Is.2. - P.76-84.

Annotation

Introduction. The histone methylation regulates gene expression and plays a role in genomic stability participating in DNA repair. Dimethylation of histone 3 lysine 36 (H3K36me2 ) is an important histone modifcation which is responsible for gene expression activation. H3K36me2 is a product of methyltransferase activity of NSD1, NSD2, NSD3, and ASH1L proteins. NSD1 mutations are known to often occur in head and neck squamous carcinoma. The presence of NSD1 mutations highly correlates with increased survival, especially for patients with laryngeal cancer. The aim of this study was an in vitro investigation of the role of NSD1 in the cell proliferation of laryngeal squamous cell cancer and non-small lung cancer cells, as well as a study of the effect of disruption of the NSD1 gene expression on cisplatin treatment response. Material and Methods. Using TCGA, correlation analysis was performed to compare NSD1 wild type and mutant patient survival. NSD1 knockout cell lines models of laryngeal and non-small cell lung cancer were developed using the CRISPR/Cas9 system. The effect of NSD1 knockout on H3K36me2 level was evaluated by western blot. Proliferation and IC50 of cisplatin in control and knockout cells were studied as well. Results. It was demonstrated that NSD1 knockout decreased the H3K36me2 level and cell proliferation in laryngeal squamous cell cancer cells and increased the sensitivity of head and neck cancer cells to cisplatin treatment, while there was no effect of NSD1 knockout in a non-small cell lung cancer cell line. Conclusion. Based on the data obtained, it can be concluded that the NSD1 protein is a potential target for inhibitor development following in vitro and in vivo testing in head-neck squamous cell carcinoma models. More studies are needed for better understanding of the regulation of tumor cell growth by NSD1.

Keywords

histone methylation, NSD1, head and neck squamous cell carcinoma, CRISPR/Cas9

The name of the journal

Siberian Journal of Oncology

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85163008752&doi=10.21294%2f1814-4861-2023-22-2-76-84&partnerID=40&md5=9259c4ca7e80ea5c7eabf9d5097495ab

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=286477&p_lang=2

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Full metadata record

Field DC	Value	Language
dc.contributor.author	Abramova Zinaida Ivanovna	ru_RU
dc.contributor.author	Bulatov Emil Rafaelevich	ru_RU
dc.date.accessioned	2023-01-01T00:00:00Z	ru_RU
dc.date.available	2023-01-01T00:00:00Z	ru_RU
dc.date.issued	2023	ru_RU
dc.identifier.citation	Topchu I.A, Tikhomirova M.V, Bulatov E.R, KNOCKOUT OF THE HISTONE METHYLTRANSFERASE NSD1 LEADS TO A DECREASE IN CELL PROLIFERATION AND AN INCREASE IN SENSITIVITY TO CISPLATIN IN LARYNGEAL SQUAMOUS CELL CARCINOMA//Siberian Journal of Oncology. - 2023. - Vol.22, Is.2. - P.76-84.	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=286477&p_lang=2	ru_RU
dc.description.abstract	Siberian Journal of Oncology	ru_RU
dc.description.abstract	Introduction. The histone methylation regulates gene expression and plays a role in genomic stability participating in DNA repair. Dimethylation of histone 3 lysine 36 (H3K36me2 ) is an important histone modifcation which is responsible for gene expression activation. H3K36me2 is a product of methyltransferase activity of NSD1, NSD2, NSD3, and ASH1L proteins. NSD1 mutations are known to often occur in head and neck squamous carcinoma. The presence of NSD1 mutations highly correlates with increased survival, especially for patients with laryngeal cancer. The aim of this study was an in vitro investigation of the role of NSD1 in the cell proliferation of laryngeal squamous cell cancer and non-small lung cancer cells, as well as a study of the effect of disruption of the NSD1 gene expression on cisplatin treatment response. Material and Methods. Using TCGA, correlation analysis was performed to compare NSD1 wild type and mutant patient survival. NSD1 knockout cell lines models of laryngeal and non-small cell lung cancer were developed using the CRISPR/Cas9 system. The effect of NSD1 knockout on H3K36me2 level was evaluated by western blot. Proliferation and IC50 of cisplatin in control and knockout cells were studied as well. Results. It was demonstrated that NSD1 knockout decreased the H3K36me2 level and cell proliferation in laryngeal squamous cell cancer cells and increased the sensitivity of head and neck cancer cells to cisplatin treatment, while there was no effect of NSD1 knockout in a non-small cell lung cancer cell line. Conclusion. Based on the data obtained, it can be concluded that the NSD1 protein is a potential target for inhibitor development following in vitro and in vivo testing in head-neck squamous cell carcinoma models. More studies are needed for better understanding of the regulation of tumor cell growth by NSD1.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject	histone methylation	ru_RU
dc.subject	NSD1	ru_RU
dc.subject	head and neck squamous cell carcinoma	ru_RU
dc.subject	CRISPR/Cas9	ru_RU
dc.title	KNOCKOUT OF THE HISTONE METHYLTRANSFERASE NSD1 LEADS TO A DECREASE IN CELL PROLIFERATION AND AN INCREASE IN SENSITIVITY TO CISPLATIN IN LARYNGEAL SQUAMOUS CELL CARCINOMA	ru_RU
dc.type	Articles in international journals and collections	ru_RU