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Role of ZBTB7A zinc finger in tumorigenesis and metastasis

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Abstract

The zinc finger and BTB (broad-complex, tramtrack and bric a brac) domain containing protein 7A (ZBTB7A) is a pleiotropic transcription factor that plays an important role in various stages of cell proliferation, differentiation, and other developmental processes. ZBTB7A is a member of the POK family that directly and specifically binds to short DNA recognition sites located near their target genes thereby acting as transcriptional activator or repressor. ZBTB7A overexpression has been associated with tumorigenesis and metastasis in various human cancer types, including breast, prostate, lung, ovarian, and colon cancer. However in some instances downregulation of ZBTB7A results in tumor progression, suggesting its role as a tumor suppressor. ZBTB7A is involved with complicated regulatory networks which include protein–protein and protein-nucleic acid interactions. ZBTB7A involvement in cancer progression and metastasis is perhaps enabled through the regulation of various signaling pathways depending on the type and genetic context of cancer. The association of ZBTB7A with other proteins affects cancer aggressiveness, therapeutic resistance and clinical outcome. This review focuses on the involvement of ZBTB7A in various signaling pathways and its role in cancer progression. We will also review the literature on ZBTB7A and cancer which could be potentially explored for its therapeutic implications.

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Abbreviations

ADH5:

Alcohol dehydrogenase 5

ADT:

Androgen deprivation therapy

AKT:

Ak strain transforming

AML:

Acute myeloid leukemia

AMP:

Adenosine monophosphate

AR:

Androgen receptor

ARF:

Alternative reading frame

AXL:

Tyrosine-protein kinase receptor

BAK1:

Bcl-2 homologous antagonist/killer 1

BAX:

BCL2 associated X, apoptosis regulator

BCL-XL :

B-cell lymphoma-extra-large

BCL-2:

B-cell lymphoma 2

BCL-6:

B-cell lymphoma 6

BCoR:

B-cell lymphoma 6 co-repressor

BIM:

Bcl-2-like protein 11

BMPs:

Bone morphogenic proteins

BTB:

Broad-complex, tramtrack and bric a brac

CBF:

Core-binding factor

CCAT2:

Colon cancer-associated transcript 2

C/EBPβ:

CCAAT/enhancer-binding protein β

CDK2:

Cyclin dependent kinase 2

CHL:

Classical Hodgkin lymphoma

CLL:

Chronic lymphocytic leukemia

CAN:

Copy number alterations

COMP:

Cartilage oligomeric matrix protein

cPARP:

Cytoplasmic poly [ADP-ribose] polymerase

CREB1:

CAMP response element binding protein

CRPC:

Castration resistant prostate cancer

CTL:

Cytotoxic T lymphocyte

DAP5:

Death-associated protein 5

Dll4:

Delta-like 4

E2F4:

E2F transcription factor 4

EIF4G2:

Eukaryotic translation initiation factor 4 gamma 2

ELK1:

ETS like-1 protein

EMT:

Epithelial-mesenchymal transition

ERα:

Estrogen receptor alpha

ERK:

Extracellular-signal-regulated kinase

ESR1:

Estrogen receptor 1

FASN:

Fatty acid synthase

FBI-1:

Factor that binds to inducer of short transcripts protein 1

FDH:

Formate dehydrogenases

FOXO:

Forkhead box transcription factor

FRE:

FBI-related element

GAS5:

Growth arrest-specific 5

GATA1:

GATA binding protein 1

GLUT3:

Glucose transporter 3

GPCR:

G-protein coupled receptor

HDACs:

Histone deacetylases

HIF-1:

Hypoxia induced factor-1

HRE:

Hypoxia related element

IKK:

IκB kinase

IL-6:

Interleukin-6

IL-24:

Interleukin-24

LINC00473:

Long intergenic non-protein coding RNA 473

lncRNAs:

Long noncoding RNAs

LRF:

Leukemia/lymphoma related factor

MBD3:

Methyl-CpG-binding domain protein 3

MCAM:

Melanoma cell adhesion molecule

M-CSF:

Macrophage colony-stimulating factor

MCT4:

Monocarboxylate transporter 4

MDM2:

Mouse double minute 2 homolog

MDR1:

Multidrug resistance 1

MEF2D:

Myocyte enhancer factor 2D

mSin3A:

SIN3 transcription regulator family member A

MKP1:

Mitogen-activated protein kinase phosphatase 1

mTOR:

Mammalian target of rapamycin

MT1-MMP:

Membrane type 1-matrix metalloproteinase

NCoR:

Nuclear receptor co-repressor

NFATc1:

Nuclear factor of activated T cells c1

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NLPHL:

Nodular lymphocyte-predominant Hodgkin lymphoma

NPC:

Nasopharyngeal carcinoma

NSCLC:

Non-small cell lung cancer

NuRD:

Nucleosome remodeling deacetylase

OSCAR:

Osteoclast associated receptor

P53:

Tumor protein P53

PAR2:

Protease‐activated receptor 2

PARP:

Poly [ADP-ribose] polymerase

PFKP:

Phosphofructokinase

Pgp:

P-glycoprotein

PICS:

PTEN loss-induced cellular senescence

PI3K:

Phosphatidylinositol-3-kinase

PKB:

Protein kinase B

PKM:

Pyruvate kinase muscle isoenzyme

POK:

POZ/BTB and Krüppel family

POZ:

Poxvirus and zinc finger

PSA:

Prostate specific antigen

PTEN:

Phosphatase and tensin homolog

rHDL:

Reconstituted high density lipoprotein

RANKL:

Receptor activator of nuclear factor kappa-Β ligand

Rb:

Retinoblastoma

RHD:

REL homology domain

RUNX1:

Runt-related transcription factor 1

RUNX1T1:

RUNX1 partner transcriptional co-repressor 1

SMAD4:

SMAD family member 4, mothers against decapentaplegic homolog 4

SMRT:

Silencing mediator of retinoic acid and thyroid hormone

SOX9:

SRY (sex determining region Y)-box transcription factor 9

Sp1:

Specificity factor 1

SRD5A1:

3-Oxo-5-alpha-steroid 4-dehydrogenase

TGF-β:

Transforming growth factor beta-1

TNFα:

Tumor necrosis factor alpha

TNFAIP3:

TNF alpha induced protein 3

TRAIL-R2:

Tumor necrosis factor-related apoptosis-inducing ligand receptor 2

TRAP:

Tartrate-resistant acid phosphatase

TRIM25:

Tripartite motif containing 25

VEGF:

Vascular endothelial growth factor

WAF1:

Wild-type P53-activated fragment 1

XAF1:

XIAP-associated factor 1

XIAP:

X-linked inhibitor of apoptosis

ZBTB:

Zinc finger and BTB

ZBTB7A:

Zinc finger and BTB domain containing protein 7A

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Acknowledgements

Efforts are supported by the Department of Defense Grants W81XWH-18-1-0618 and W81XWH-19-1-0720 to SG. SK acknowledges University Grants Commission, India and Department of Science and Technology, India for providing financial support in the form of UGC-BSR Research Start-Up-Grant [No. F.30–372/2017 (BSR)] and DST-SERB Grant [EEQ/2016/000350]. SK acknowledges Central University of Punjab, Bathinda, India for providing Research Seed Money Grant [GP-25]. AKS, and KSP acknowledge CSIR-India, and DBT-India funding agencies for providing financial assistance in the form of Senior Research Fellowship. PPK and MS acknowledge Indian Council of Medical research for the financial support in the form of Senior Research fellowships [FileNo.5/3/8/81/ITR-F/2020, and FileNo.5/3/8/80/ITR-F/2020-ITR respectively].

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Authors and Affiliations

  1. Molecular Signaling and Drug Discovery Laboratory, Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151401, India

    Atul Kumar Singh, Prem Prakash Kushwaha, Kumari Sunita Prajapati, Mohd Shuaib & Shashank Kumar

  2. Department of Urology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA

    Shiv Verma & Sanjay Gupta

  3. Department of Urology, The Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA

    Shiv Verma & Sanjay Gupta

  4. Department of Nutrition, Case Western Reserve University, Cleveland, OH, 44106, USA

    Sanjay Gupta

  5. Divison of General Medical Sciences, Case Comprehensive Cancer Center, Cleveland, OH, 44106, USA

    Sanjay Gupta

  6. Department of Urology, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, 44106, USA

    Sanjay Gupta

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  1. Atul Kumar Singh
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  2. Shiv Verma
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AKS, SV, SK, and SG have made substantial contributions to conception and writing of the manuscript. The figures and tables were developed by PPK, KSP, MS, AKS and SS. SV made substantial contributions to conception and data analysis from TCGA and other bio-portals and its interpretation. SG provided administrative, technical, and material support.

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Singh, A.K., Verma, S., Kushwaha, P.P. et al. Role of ZBTB7A zinc finger in tumorigenesis and metastasis. Mol Biol Rep 48, 4703–4719 (2021). https://doi.org/10.1007/s11033-021-06405-x

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