Retinal determination gene networks: from biological functions to therapeutic strategies

Zhu, Shuangli; Li, Wanling; Zhang, Hao; Yan, Yuheng; Mei, Qi; Wu, Kongming

doi:10.1186/s40364-023-00459-8

Biomarker Research

Table 1 Summarization of targets regulated by RDGN

From: Retinal determination gene networks: from biological functions to therapeutic strategies

RDGN member	Disease	Mechanism	Function	Reference
DACH1	CRC (Organoid)	Interact with SMAD4 and inhibit BMP signaling	Inhibit cell proliferation, stemness and tumorigenesis	[17]
		Inhibit the expression of Wnt signaling downstream targets (c-Myc and cyclinD1)	Suppress CRC growth	[18]
		Inhibit TGF-β signaling	Inhibit migration and invasion of CRC	[19]
	BC	Down-regulating the transcription of MMP-9	Inhibit BC cell invasion and metastasis	[20]
		Inhibit the transcriptional activity of SNAI1	Repress breast carcinoma metastasis	[21]
		Decrease the level of CD44	Suppress BC progression	[22]
		Block YB-1	Represses YB-1-mediated oncogenic transcription and translation	[23]
		Bind to p53	Inhibit BC contact-independent growth	[24]
		Suppress IL-8	Inhibit BC cellular migration and invasion	[8]
		Inhibit TGF-β signaling	Inhibit TGF-β-induced apoptosis	[25]
	NSCLC	CXCL1	Predict poor prognosis of ADC	[26]
	ADC	CXCL5	Inhibit ADC invasion and tumor growth	[27]
		CXCL8	Repress tumorigenesis; improve prognosis	[28]
		Bind p53	Block the growth of ADC cells	[29]
		Downregulate of peroxiredoxin 3	Inhibit the proliferation and invasion of ADC	[30]
	EC	Activat TGF-β signaling	Inhibit esophageal cancer growth	[31]
	EC	CXCL1/2	Inhibit NF-κB and reducing MDSC migration	[32]
	GC	Inhibit TGF-β signaling	Inhibit the invasion and metastasis of GC	[33]
	RCC	Inhibit cyclin D1 expression	Inhibit cellular proliferation and tumor growth	[34]
	HCC	Up-regulat p53 expression	Suppress the progression of HCC	[35]
	HCC	Reactivate TGF-β signaling	Suppress cellular growth	[36]
	endometrial carcinoma	Inhibite Notch1 pathway via c-Jun	Reverse MPA resistance and EMT	[37]
DACH1	OC	Inhibit TGF-β signaling	Inhibit OC progression	[38]
	Gliomas	Inhibit TGF-β signaling; IL-6; FGF	Inhibit tumor-initiating activity of glioma cells	[39]
	PC	CXCL1/2; CXCL5; CXCL8; IL-6; FGF	Inhibit PC cells growth and migration	[9, 40]
	Artery genesis	CXCL12	Stimulate shear stress-guided endothelial cell migration and coronary artery growth	[41]
	Artery genesis	Inhibit the expression of FABP4, by endothelial Notch signaling	Result in the occurrence of cardiac hypertrophy	[42,43,44]
	diabetes	rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion	Cause familial young-onset diabetes, pre-diabetes	[11]
	Renal hypodysplasia	carrying homozygous missense mutations in both BMP4 (p.N150K) and DACH1 (p.R684C)	Cause renal hypodysplasia	[45]
DACH2	Myogenesis	Indirectly upregulated and activates Murf1 and Atrogin1 expression	Cause muscle atrophy	[46,47,48]
SIX1	BC	Activate TGF-β signaling	Induce properties of EMT	[49, 50]
	BC	Activate MAPK and TGF signaling pathways	Mediate the accumulation of CSCs	[49]
	BC	Upregulate VEGF-C	Induce lymphangiogenesis and metastasis	[51]
	CC	Activate TGF-β signaling	Promote EMT, CSCs properties and malignant conversion	[52]
	CC	Upregulate VEGF-C	Promote tumor lymphangiogenesis	[53]
	EC	Activate TGF-β signaling	Promote tumor cells growth	[54]
	OC	Downregulate TRAIL	Cause resistance to TRAIL-mediated apoptosis and is associated with poor survival	[55]
	HCC	Bind to p53	Promote HCC progression	[35]
	HCC	IL-6/STAT3/MMP-9	Facilitate HCC cells invasion	[56]
	rhabdomyosarcoma	Activate cyclin D1 transcription	Lead to tumor initiation	[57]
	lung fibrosis	Increase the level of MIF	Promote lung fibrosis	[58]
	asthma	MMP-9; MMP-2	Suppress airway inflammation and remodeling	[59]
SIX1	erythroleukemia	Strengthen GATA1 function	Accelerate erythropoiesis	[60]
	AML	Block Wnt/SIX1 signaling	Suppress the progression of AML	[61]
	Myogenesis	SIX genes are expressed throughout muscle development	participate in the genesis and the maintenance of myofibers diversity	[62]
EYA	BC	Induce TGF-β signaling	Promote the metastasis of tumor cells	[63]
	BC	Dephosphorylate PP2A-B55α	Increase cancer cells' metastasis capability	[64]
	cardiac hypertrophy	EYA2 activates mTOR signaling pathway	Cause cardiac physiological hypertrophy	[65]
	cardiac hypertrophy	EYA4 mutation	Cause dilated cardiomyopathy	[66]
	BOR syndrome	mutation in SIX and EYA or disruption of the SIX/EYA complex	cause BOR syndrome	[67,68,69]

Abbreviations: BMP Bone morphogenetic protein, CRC Colorectal cancer, CXCL C-X-C motif ligand, BC Breast cancer, MMP-9 Matrix metalloproteinase 9, NSCLC Non-small cell lung cancer, ADC Lung adenocarcinoma, EC Esophageal cancer, GC Gastric cancer, RCC Renal cell carcinoma, HCC Hepatocellular carcinoma, TGF-β Transforming growth factor beta, MPA Medroxyprogesterone acetate, EMT Epithelial to mesenchymal transition, IL-8 Interleukin-8, OC Ovarian cancer, PC Prostate cancer, MDSC Myeloid-derived suppressive cell, FGF Fibroblast growth factor, CC Cervical cancer, CSC Cancer stem cells, TRAIL Tumor necrosis factor-related apoptosis-inducing ligand, AML Acute myeloid leukemia, PP2A Protein phosphatase 2A, BOR Branchio-oto-rena

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ISSN: 2050-7771

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