PMID- 36037675
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20220921
IS  - 1878-3279 (Electronic)
IS  - 0171-2985 (Linking)
VI  - 227
IP  - 5
DP  - 2022 Sep
TI  - Involvement of Xeroderma Pigmentosum Complementation Group G (XPG) in epigenetic 
      regulation of T-Helper (T(H)) cell differentiation during breast cancer.
PG  - 152259
LID - S0171-2985(22)00085-7 [pii]
LID - 10.1016/j.imbio.2022.152259 [doi]
AB  - TNFalpha and IFN-gamma secreted by CD4(+)T-Helper (T(H)) cells have antitumor activity 
      followed by polarisation of T(H)1 phenotype in response to IL-12 secreted by 
      dendritic cells, inducing expression of XPG, Nucleotide-Excision Repair (NER) 
      complex component, which is downregulated in breast cancer. Therefore, we 
      investigated the involvement of XPG in T(H)-cell differentiation in breast 
      cancer. XPG knock-out (KO) PBMC and T(H)1 polarised CD4(+) T(H)-cells isolated 
      from breast cancer and control subjects blood samples were used to observe mRNA 
      expressions of associated genes, % enrichment of corresponding epigenetic 
      markers, and m6A RNA methylation levels to study the molecular mechanisms 
      involved. Assays to investigate Cytotoxic T Lymphocyte (CTL) activity after 
      cross-checking extracellular secretion levels. Our XPGKO results indicated 
      upregulation of T(H)2 and Treg, downregulation of T(H)1, and negligible change 
      for T(H)17; reduced expression of genes associated with tumour suppression (TP53, 
      BRCA1) and DNA repair (H2AFX, ATM) for breast cancer T(H)-cells. CTCF associated 
      T(H)1 specific function, reduced %enrichment of XPG, CSA, and ERCC1, increased 
      %enrichment of gammaH2A.X, and altered histone modifications (methylation, 
      deacetylation) at the IFN-gamma gene locus in XPGKO breast cancer T(H)1-cells. 
      Increased m6A RNA methylation mediated by XPG leads to T(H)1 cell specificity, 
      further inducing CTL activity by releasing extracellular IFG-gamma, which activates 
      CD8(+) CTLs. This article explores the association of the vital NER protein, XPG 
      with the epigenetic modifications behind T(H)1 cell differentiation, augmenting 
      the expressions of T(H)1-network genes to evoke protective immunity in breast 
      cancer.
CI  - Copyright (c) 2022 Elsevier GmbH. All rights reserved.
FAU - Pal, Riasha
AU  - Pal R
AD  - Department of Biotechnology, SRM Institute of Science and Technology, 
      Kattankulathur, Tamil Nadu 603203, India.
FAU - Rakshit, Sudeshna
AU  - Rakshit S
AD  - Department of Biotechnology, SRM Institute of Science and Technology, 
      Kattankulathur, Tamil Nadu 603203, India.
FAU - Shanmugam, Geetha
AU  - Shanmugam G
AD  - Department of Biotechnology, SRM Institute of Science and Technology, 
      Kattankulathur, Tamil Nadu 603203, India.
FAU - Paul, Nilanjan
AU  - Paul N
AD  - Department of Biotechnology, SRM Institute of Science and Technology, 
      Kattankulathur, Tamil Nadu 603203, India.
FAU - Bhattacharya, Deep
AU  - Bhattacharya D
AD  - Department of Biotechnology, SRM Institute of Science and Technology, 
      Kattankulathur, Tamil Nadu 603203, India.
FAU - Chatterjee, Arya
AU  - Chatterjee A
AD  - Department of Biotechnology, SRM Institute of Science and Technology, 
      Kattankulathur, Tamil Nadu 603203, India.
FAU - Singh, Arunangsu
AU  - Singh A
AD  - Department of Biotechnology, SRM Institute of Science and Technology, 
      Kattankulathur, Tamil Nadu 603203, India.
FAU - George, Melvin
AU  - George M
AD  - Department of Clinical Pharmacology, SRM Medical College Hospital and Research 
      Centre, Kattankulathur, Tamil Nadu 603203, India.
FAU - Sarkar, Koustav
AU  - Sarkar K
AD  - Department of Biotechnology, SRM Institute of Science and Technology, 
      Kattankulathur, Tamil Nadu 603203, India. Electronic address: 
      koustavsarkar@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220822
PL  - Netherlands
TA  - Immunobiology
JT  - Immunobiology
JID - 8002742
RN  - 63231-63-0 (RNA)
RN  - Xeroderma Pigmentosum, Complementation Group G
SB  - IM
MH  - *Breast Neoplasms/genetics
MH  - Cell Differentiation/genetics
MH  - Epigenesis, Genetic
MH  - Female
MH  - Humans
MH  - Leukocytes, Mononuclear/metabolism
MH  - RNA
MH  - Th1 Cells
MH  - *Xeroderma Pigmentosum/genetics/metabolism
OTO - NOTNLM
OT  - Breast cancer
OT  - Epigenetic modifications
OT  - NER
OT  - T(H)-cell
OT  - XPG
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/08/30 06:00
MHDA- 2022/09/09 06:00
CRDT- 2022/08/29 18:24
PHST- 2021/12/27 00:00 [received]
PHST- 2022/08/03 00:00 [revised]
PHST- 2022/08/13 00:00 [accepted]
PHST- 2022/08/30 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/08/29 18:24 [entrez]
AID - S0171-2985(22)00085-7 [pii]
AID - 10.1016/j.imbio.2022.152259 [doi]
PST - ppublish
SO  - Immunobiology. 2022 Sep;227(5):152259. doi: 10.1016/j.imbio.2022.152259. Epub 
      2022 Aug 22.