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] | |
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] | |
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 | ||
Artery genesis | CXCL12 | Stimulate shear stress-guided endothelial cell migration and coronary artery growth | [41] | |
Inhibit the expression of FABP4, by endothelial Notch signaling | Result in the occurrence of cardiac hypertrophy | |||
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 | |
SIX1 | BC | Activate TGF-β signaling | Induce properties of EMT | |
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] |
Dephosphorylate PP2A-B55α | Increase cancer cells' metastasis capability | [64] | ||
cardiac hypertrophy | EYA2 activates mTOR signaling pathway | Cause cardiac physiological hypertrophy | [65] | |
EYA4 mutation | Cause dilated cardiomyopathy | [66] | ||
BOR syndrome | mutation in SIX and EYA or disruption of the SIX/EYA complex | cause BOR syndrome |