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Table 1 Summary of RFX1 targets showing the pleiotropic nature of the RFX1 transcription factor

From: RFX1: a promising therapeutic arsenal against cancer

Target gene/Protein

Target gene/Protein function

RFX1 mediated regulation

Outcome

Refs.

Id2

Repression of helix-loop-helix transcription factors

Rapid increase in Id2 expression upon growth serum stimulation in the NIH3T3 mouse embryo fibroblast cell line

[1]

HBV gene

Viral replication

Induces HBV gene enhancer activity, especially in liver

[36]

MHC class II genes

Antigen presentation; Adaptive immunity; Self-tolerance

 

[11, 12]

ITGA6

Testis cord development

Critical for proper spermatogenesis in mouse

[46]

MCP1

Monocyte and basophil chemotactic

RFX1 regulated MCP1 is a potential therapeutic strategy for CAD management

[68]

CD70

CD27 ligand; Co-stimulatory signaling

RFX1 increased H3K9 tri-methylation

[153]

ITGAL / CD11a

Cell adhesion; Co-stimulatory signaling

RFX1 increased H3K9 tri-methylation

[153]

TLR4

Activation of innate immune system

RFX1 can regulate innate immunity response and is a potential target for CAD management

[14]

FGF1

Cell proliferation; Neurogenesis

RFX1 disrupts senescence of glioblastoma stem cells by targeting FGF1

[7]

TGF-β2

Wide variety of roles from cell proliferation, motility, differentiation and apoptosis

RFX1 suppresses TGFβ2-ERK signaling pathway and resultant cell proliferation in neuroblastoma cell lines

[139]

COL1A1

Type I collagen fiber

RFX1 binds to methylated COL1A1 near transcription start site

[154]

COL1A2

Type I collagen fiber

RFX1/ MDBP complex binds to the methylated first exon of COL1A2 promoter and recruits HDAC1 and mSin3 enzymes

[64, 154, 155]

CDX2

Intestinal cell growth and differentiation

Rfx1 downregulation coupled with CDX2 overexpression is key in adenocarcinoma tumor progression

[3]

c-Abl

Signal transducer; Proto-oncogene

RFX1 directly interacts and potentiates c-Abl kinase activity

[56]

CD44

Cell surface receptor

RFX1 prevents metastasis of multiple glioblastoma cell lines

[2]

IL-17A

Pro-inflammatory cytokine

RFX1 increased H3K9 tri-methylation and decreased H3 acetylation at IL17A promoter

[15]

RFX1

Context dependent transcription factor

Auto-repression of RFX1 in response to DNA damage

[86]

c-Myc

DNA binding protein; Proto-oncogene;

RFX1 mediated c-Myc downregulation was observed in differentiated HL60 cell line human leukemia cell line

[9]

PCNA

Involved in DNA replication and repair pathways

 

[156, 157]

IL5RA

Receptor for IL5

 

[16]

PTPN6/SHP1

Cell signaling, differentiation

RFX1/AP4 mediated SHP-1 regulation reduced MCF-7 cell proliferation

[81]

MCL1

Anti-apoptotic factor

RFX1/SHP-1/STAT3/MCL1 axis of autophagy in HCC cells

[10]

EAAT3

Glutamate uptake

RFX1 upregulates EAAT3 in rat neurons and could have treatment applications in neurological disorders

[158]

SPATA4

Spermatogenesis; Modulates cell proliferation, differentiation and apoptosis in many cells

Downregulate Sertoli cell proliferation

[159]

PNRC

Nuclear receptor co-activator

 

[160]

rpL30

Ribosomal protein

 

[139]

DNAAF4/DYX1C1

Neuronal migration

RFX1 regulates one of the most replicated candidate genes of Ciliary dyslexia

[161]

DCDC2

Neuronal migration

RFX1 regulates one of the most replicated candidate genes of Ciliary dyslexia

[161]

  1. : Down regulation
  2. : Upregulation
  3. Id2 inhibitor of DNA binding 2, HBV human hepatitis B virus enhancer I, ITGA6 integrin alpha-6, MCP1 Monocyte chemoattractant protein, CAD Coronary artery disease, CD70 Cluster of Differentiation 70, ITGAL / CD11a integrin subunit alpha L, FGF1 fibroblast growth factor 1, COL1A Collagen α1(I) Gene, COL1A2 collagen type I alpha 2, CDX2 Caudal type homeobox 2, PTPN6/SHP1 protein tyrosine phosphatase non-receptor type 6/ Src homology region 2 domain-containing phosphatase-1, PCNA proliferating cell nuclear antigen, EAAT3 Excitatory amino acid transporter type 3, SPATA4 spermatogenesis associated 4, PNRC Proline-rich Nuclear Receptor Coactivator, rpL30 ribosomal protein L30, DNAAF4/ DYX1C1 dynein axonemal assembly factor 4/ dyslexia 1 candidate 1 gene, DCDC2 doublecortin domain-containing 2 gene