Association of Wiskott-Aldrich syndrome protein (WASp) in epigenetic regulation of B cell differentiation in non-small-cell lung cancer (NSCLC).

Publisher: Springer Country of Publication: United States NLM ID: 9435512 Publication Model: Electronic Cited Medium: Internet ISSN: 1559-131X (Electronic) Linking ISSN: 13570560 NLM ISO Abbreviation: Med Oncol Subsets: MEDLINE

Publication: 2011- : New York : Springer
Original Publication: Northwood, Middlesex, England : Science and Technology Letters, c1994-

Carcinoma, Non-Small-Cell Lung*/genetics ; Lung Neoplasms*/genetics ; Wiskott-Aldrich Syndrome Protein*/genetics ; Wiskott-Aldrich Syndrome Protein*/metabolism; Female ; Humans ; Male ; Cell Differentiation/genetics ; Cytokines/metabolism ; Epigenesis, Genetic ; Histones/metabolism ; Transcription Factors/genetics ; B-Lymphocytes/metabolism

Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer which is the deadliest type of cancer for both men and women. Previous studies already showed that cell-intrinsic loss of WASp causes B cell tolerance and WASp deficiency in T helper (T H ) cells is linked to negative effects on cytokine gene transcription necessary for T H 1 differentiation. In the current study, we investigated the molecular mechanisms involved in WASp-mediated epigenetic regulation of B cell differentiation during NSCLC. Our ChIP-qPCR data suggest the less percentage enrichment of the B cell differentiating factors (Ikaros, Pax5, PU.1, BATF) and WASp across the WAS gene in the B cells of NSCLC patients in comparison with normal healthy donors and overexpression of WASp showed the reverse effects. WASp-depleted B cells while co-culturing with respective PBMCs isolated from normal healthy donors and NSCLC patients, we observed upregulation of T H 2-, T H 17-, and Treg-specific cytokines (IL4, ILI7A, IL10) & transcription factors (GATA3, RORC, FOXP3) and downregulation of T H 1-specific cytokine (IFNγ) & transcription factor (TBX21). Our study showed that the overexpression of WASp resulted into upregulation of B cell differentiating factors, tumor suppressor protein (p53), histone methylation marker (H3K4me3) with concomitant downregulation of tumor-promoting factors (Notch 1, β-Catenin, DNAPKcs) and histone deacetylation marker (HDAC2) and increase in percentage cytotoxicity of NSCLC-specific cells (A549). Successful overexpression of WASp not only helps in epigenetic regulation of B cell differentiation but also supports tumor suppression in NSCLC. Thus, WASp can be targeted for therapeutic intervention of NSCLC.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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ECR/2016/000965 Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Govt. of India

Keywords: B cell differentiating factors; B cells; Cytokines; Epigenetics; Non-small-cell lung cancer (NSCLC); T helper (TH) cells; Tumor suppressor; Wiskott-Aldrich syndrome protein (WASp)

0 (Cytokines)
0 (Histones)
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0 (Wiskott-Aldrich Syndrome Protein)

Date Created: 20231225 Date Completed: 20231227 Latest Revision: 20240328

20240329

10.1007/s12032-023-02264-7

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