basic FUNCTION
| architectural transcription factor |
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organizing the framework of nucleoprotein-DNA transcriptional complex |
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regulates expression of many important repressors of E-cadherin (CDH1) |
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playing a role in leukemogenesis |
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involved in regulation of cell proliferation |
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playing a role in adipogenesis, osteogenesis, and general growth control |
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having a critical function in cardiogenesis |
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acts in a gene-specific manner to orchestrate the transcriptional network necessary for the epithelial-mesenchymal transition program |
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chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells |
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tissue-specific expression and transcription level of HMGA2 during inner ear development, suggesting its potential dual role in early differentiation and maintenance of both hair and supporting cell phenotypes |
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directly regulates GATA6 and thereby modulates FZD2 expression |
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critical role for HMGA2 in promoting EMT, migration, invasion, and proliferation of colon cancer cells |
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HMGA2-induced apoptosis was likely dependent on the pathway of DNA damage |
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played an important role in the progression of bladder cancer |
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non-histone chromatin binding protein that plays important roles in the repair and protection of genomic DNA in embryonic stem cells and cancer cells |
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novel role of HMGA2 in telomere protection and promoting telomere stability in cancer cells |
CELLULAR PROCESS
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nucleotide, chromatin organization
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| nucleotide, transcription, regulation
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a component
| HMGA2-IGF2BP2 axis functions as a key regulator of satellite cell activation and therefore skeletal muscle development |
protein
| directly binds to the SNAI1 promoter and acts as a transcriptional regulator of SNAI1 expression |
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LUM, a tumor suppressor that inhibits epithelial-to-mesenchymal transition(EMT), is transcriptionally repressed by HMGA2 and frequently lost in human high-grade serous papillary carcinoma |
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CKAP4 is required for stabilizing DICER1 protein and for optimal regulation of a reporter gene coupled to the 3prime untranslated region of HMGA2 mRNA in human cells |
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PEBP1 inhibits syndecan-2 (SDC2), which is aberrantly expressed in breast cancer, via downregulation of HMGA2 |
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HMGA2-mediated direct regulation of GATA6 is crucial for fine-tuning the activity of WNT signaling in the airway epithelium |
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HMGA2 positively regulates the SNAI2 expression by directly binding to the regulatory region in SNAI2 promoter |
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interaction of HMGA2 with the key shelterin protein TERF2 |
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FGF2, a growth factor commonly used to promote self-renewal in Mesenchymal stem cells (MSCs), rapidly induces HMGA2 expression in a time- and concentration-dependent manner |
activated by
| OTX2 and HMGA2 protein binds to the enhancers targeted by OTX2, thus facilitating the engagement and/or the stable association of OTX2 |
Other morbid association(s)
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Type | Gene Modification | Chromosome rearrangement | Protein expression | Protein Function
|
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tumoral
| fusion
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|  
|  
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RAD51L/HMGIC fusion, HEI1/HMGIC t(14;12)in uterine leiomyoma | tumoral
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| translocation
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|  
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t(3;12),t(12;3),t(12;4),t(8;12) in benign mesenchymal tumors (see RATT, MAR, ERV5, ALDH2, ULCR12, LPP, LHFP, COX6C), see also TSG12A) | tumoral
|  
| amplification
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|  
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in well differentiated liposarcoma | tumoral
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| --over
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in myelofibrosis with myeloid metaplasia and in uterine leiomyoma (associated with loss of TSC2 function) | tumoral
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|  
| --over
|  
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in thyroid carcinomas | tumoral
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| --over
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increased HMGA2 expression in uterine leiomyomas with 12q14-15 rearrangements | tumoral
|  
|  
| --over
|  
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in polycythemia vera with t(12;21)(q14;q22) | constitutional
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|  
| --other
|  
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rearrangement of HMGA1 and HMGA2 genes likely contributes to endometriosis | tumoral
|  
|  
| --over
|  
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in human ovarian carcinomas | tumoral
|  
|  
| --over
|  
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common in both early and late-stage high-grade ovarian serous papillary carcinoma | tumoral
|  
|  
| --over
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through its relationship to epithelial-mesenchymal transition (EMT), thus seems to aggravate invasion and metastasis in gastric cancer | |
Susceptibility
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to variation of adult and childhood height in the general population to uterine leyomyomatosis (UL) and decreased height to type 2 diabetes |
Variant & Polymorphism
SNP
, other
| common variant is associated with adult and childhood height in the general population |
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a specific TC dinucleotide repeat (TC227) in the 5 UTR of HMGA2 with both predisposition to UL with decreased height |
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increasing the risk of type 2 diabetes |
|
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Candidate gene
| for growth restriction in del 12q14 syndrome |
Marker
Therapy target
|
System | Type | Disorder | Pubmed |
cancer | reproductive | ovary | |
represents a promising target for gene silencing therapy in ovarian cancer | cancer | urinary | | |
target for therapy in human bladder cancer | cancer | digestive | colon | |
a potential molecular target to prevent colon cancer progression |
| | |
| diet induced obsity in (-/-) mice | |
Hmga2 knockout mice exhibit impaired muscle development and reduced myoblast proliferation, while overexpression of Hmga2 promotes myoblast growth |