Genomes and Genes
Summary: An AT-hook-containing (AT-HOOK MOTIFS) nuclear protein that is expressed predominantly in proliferating and undifferentiated mesenchymal cells.
- Sarhadi V, Wikman H, Salmenkivi K, Kuosma E, Sioris T, Salo J, et al. Increased expression of high mobility group A proteins in lung cancer. J Pathol. 2006;209:206-12 pubmed..As HMGA proteins were expressed in about 90% of lung carcinomas and their expression was inversely associated with survival, they may provide useful markers for lung cancer diagnosis and prognosis. ..
- Nishino J, Kim I, Chada K, Morrison S. Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression. Cell. 2008;135:227-39 pubmed publisher..Hmga2 thus promotes fetal and young-adult stem cell self-renewal by decreasing p16(Ink4a)/p19(Arf) expression. Changes in let-7 and Hmga2 expression during aging contribute to the decline in neural stem cell function. ..
- Hristov A, Cope L, Reyes M, Singh M, Iacobuzio Donahue C, Maitra A, et al. HMGA2 protein expression correlates with lymph node metastasis and increased tumor grade in pancreatic ductal adenocarcinoma. Mod Pathol. 2009;22:43-9 pubmed publisher..Using tissue microarrays generated from 124 pancreatic ductal adenocarcinoma cases, we also assessed HMGA2 protein levels by immunohistochemical analysis...
- Meyer B, Loeschke S, Schultze A, Weigel T, Sandkamp M, Goldmann T, et al. HMGA2 overexpression in non-small cell lung cancer. Mol Carcinog. 2007;46:503-11 pubmed..05). The results presented herein indicate that HMGA2 overexpression is a common event in NSCLC and could serve as molecular marker for lung cancer. ..
- Abe N, Watanabe T, Suzuki Y, Matsumoto N, Masaki T, Mori T, et al. An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue. Br J Cancer. 2003;89:2104-9 pubmed..Based on these findings, we propose that an increased expression level of the HMGA2 protein is closely associated with the malignant phenotype in the pancreatic exocrine system, and accordingly, HMGA2 ..
- Piscuoglio S, Zlobec I, Pallante P, Sepe R, Esposito F, Zimmermann A, et al. HMGA1 and HMGA2 protein expression correlates with advanced tumour grade and lymph node metastasis in pancreatic adenocarcinoma. Histopathology. 2012;60:397-404 pubmed publisher..No, or very low, expression was found in normal pancreatic tissue. Our results suggest that HMGA1 and HMGA2 are implicated in pancreatic carcinogenesis and may play a role in tumour progression towards a more malignant phenotype. ..
- Noro B, Licheri B, Sgarra R, Rustighi A, Tessari M, Chau K, et al. Molecular dissection of the architectural transcription factor HMGA2. Biochemistry. 2003;42:4569-77 pubmedb>HMGA2 protein belongs to the High Mobility Group A (HMGA) family of architectural transcription factors...
- Markowski D, Helmke B, Meyer F, von Ahsen I, Nimzyk R, Nolte I, et al. BMP4 increases expression of HMGA2 in mesenchymal stem cells. Cytokine. 2011;56:811-6 pubmed publisher..Thus, we propose that in adipose tissue BMP4 acts in part by activating HMGA2 making this architectural transcription factor one of the major downstream players in that system...
- Winslow M, Dayton T, Verhaak R, Kim Kiselak C, Snyder E, Feldser D, et al. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature. 2011;473:101-4 pubmed publisher..Thus, the oncogenic and suppressive functions of Nkx2-1 in the same tumour type substantiate its role as a dual function lineage factor. ..
- Zhou X, Benson K, Przybysz K, Liu J, Hou Y, Cherath L, et al. Genomic structure and expression of the murine Hmgi-c gene. Nucleic Acids Res. 1996;24:4071-7 pubmed..Since the human homolog is disrupted in a number of tumors, HMGI-C could play an important role in cell proliferation and differentiation during mammalian development. ..
- Li O, Vasudevan D, Davey C, Droge P. High-level expression of DNA architectural factor HMGA2 and its association with nucleosomes in human embryonic stem cells. Genesis. 2006;44:523-9 pubmed
- Sanna S, Jackson A, Nagaraja R, Willer C, Chen W, Bonnycastle L, et al. Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Genet. 2008;40:198-203 pubmed publisher..44 cm (overall P < 10(-15)). Our results indicate that there may be a link between the genetic basis of height and osteoarthritis, potentially mediated through alterations in bone growth and development. ..
- Park S, Shell S, Radjabi A, Schickel R, Feig C, Boyerinas B, et al. Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2. Cell Cycle. 2007;6:2585-90 pubmed..The late repression of HMGA2 by let-7 during embryonic development, and the early reexpression of HMGA2 during cancer development, is in line with the hypothesis that cancer development represents a case of reverse embryogenesis. ..
- Cui T, Leng F. Specific recognition of AT-rich DNA sequences by the mammalian high mobility group protein AT-hook 2: a SELEX study. Biochemistry. 2007;46:13059-66 pubmed..Identification of the consensus sequences for HMGA2 represents an important step toward finding its binding sites within the genome. ..
- Li O, Li J, Droge P. DNA architectural factor and proto-oncogene HMGA2 regulates key developmental genes in pluripotent human embryonic stem cells. FEBS Lett. 2007;581:3533-7 pubmed..Our results establish HMGA2 as a regulator of human genes linked to mesenchymal cell differentiation, adipogenesis, and hES cell growth. ..
- Lee Y, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 2007;21:1025-30 pubmed
- Chiappetta G, Ferraro A, Vuttariello E, Monaco M, Galdiero F, De Simone V, et al. HMGA2 mRNA expression correlates with the malignant phenotype in human thyroid neoplasias. Eur J Cancer. 2008;44:1015-21 pubmed publisher..b>HMGA2 protein was detectable in four out of 21 follicular carcinomas, 30 out of 45 papillary carcinomas, and 11 out of 12 ..
- Henriksen J, Stabell M, Meza Zepeda L, Lauvrak S, Kassem M, Myklebost O. Identification of target genes for wild type and truncated HMGA2 in mesenchymal stem-like cells. BMC Cancer. 2010;10:329 pubmed publisher..that are affected by sarcoma-associated variants of HMGA2, we have over-expressed wild type and truncated HMGA2 protein in an immortalized mesenchymal stem-like cell (MSC) line, and investigated the localisation of these proteins ..
- Li A, Lin H, Kuo C, Shih H, Wang C, Yen Y, et al. High-mobility group A2 protein modulates hTERT transcription to promote tumorigenesis. Mol Cell Biol. 2011;31:2605-17 pubmed publisher..These findings are potentially clinically relevant, because HMGA2 expression is reported to be upregulated in a number of human cancers as telomere maintenance is essential for tumorigenesis. ..
- ..This review summarizes the recent progress made using genome-wide association studies on the identification of common genetic variants that contribute to adult height variation in the general population. ..
- Thuault S, Valcourt U, Petersen M, Manfioletti G, Heldin C, Moustakas A. Transforming growth factor-beta employs HMGA2 to elicit epithelial-mesenchymal transition. J Cell Biol. 2006;174:175-83 pubmed..This network of signaling/transcription factors that work sequentially to establish EMT suggests that combinatorial detection of these proteins could serve as a new tool for EMT analysis in cancer patients. ..
- Di Cello F, Hillion J, Hristov A, Wood L, Mukherjee M, Schuldenfrei A, et al. HMGA2 participates in transformation in human lung cancer. Mol Cancer Res. 2008;6:743-50 pubmed publisher..In addition, there is a statistically significant correlation between HMGA2 protein staining by immunohistochemical analysis and tumor grade (P < 0.001)...
- Meza Zepeda L, Berner J, Henriksen J, South A, Pedeutour F, Dahlberg A, et al. Ectopic sequences from truncated HMGIC in liposarcomas are derived from various amplified chromosomal regions. Genes Chromosomes Cancer. 2001;31:264-73 pubmed..Some of the ectopic sequences were transcribed in other tissues, and most of the ectopic sequences also showed recurrent amplification in liposarcomas. ..
- Anand A, Chada K. In vivo modulation of Hmgic reduces obesity. Nat Genet. 2000;24:377-80 pubmed..Our studies implicate a role for HMGIC in fat-cell proliferation, indicating that it may be an adipose-specific target for the treatment of obesity. ..
- Crombez K, Vanoirbeek E, Van de Ven W, Petit M. Transactivation functions of the tumor-specific HMGA2/LPP fusion protein are augmented by wild-type HMGA2. Mol Cancer Res. 2005;3:63-70 pubmed..These results support the concept that the transactivation functions of the novel HMGA2/LPP transcription factor contribute to lipomagenesis. ..
- Ligon A, Moore S, Parisi M, Mealiffe M, Harris D, Ferguson H, et al. Constitutional rearrangement of the architectural factor HMGA2: a novel human phenotype including overgrowth and lipomas. Am J Hum Genet. 2005;76:340-8 pubmed..Systematic genetic analysis and clinical studies of this child may offer unique insights into the role of HMGA2 in adipogenesis, osteogenesis, and general growth control...
- Pierron A, Fernandez C, Saada E, Keslair F, Hery G, Zattara H, et al. HMGA2-NFIB fusion in a pediatric intramuscular lipoma: a novel case of NFIB alteration in a large deep-seated adipocytic tumor. Cancer Genet Cytogenet. 2009;195:66-70 pubmed publisher..Both the truncation of HMGA2 and the nature of its fusion partner gene might be relevant in the adipose tissue tumorigenesis. ..
- Brants J, Ayoubi T, Chada K, Marchal K, Van de Ven W, Petit M. Differential regulation of the insulin-like growth factor II mRNA-binding protein genes by architectural transcription factor HMGA2. FEBS Lett. 2004;569:277-83 pubmed..Our results clearly indicate that HMGA2 differentially regulates expression of IMP family members during embryogenesis. ..
- Manfioletti G, Giancotti V, Bandiera A, Buratti E, Sautiere P, Cary P, et al. cDNA cloning of the HMGI-C phosphoprotein, a nuclear protein associated with neoplastic and undifferentiated phenotypes. Nucleic Acids Res. 1991;19:6793-7 pubmed..Analysis of mRNA levels demonstrate that the HMGI-C gene is not expressed in a variety of mouse tissues but is expressed in Lewis lung carcinoma cells. ..
- Fedele M, Battista S, Kenyon L, Baldassarre G, Fidanza V, Klein Szanto A, et al. Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas. Oncogene. 2002;21:3190-8 pubmed..These transgenic mice may represent an important tool for the study of this kind of neoplasia. ..
- Narita M, Narita M, Krizhanovsky V, Nũnez S, Chicas A, Hearn S, et al. A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell. 2006;126:503-14 pubmed..Our results identify a component of the senescence machinery that contributes to heterochromatin formation and imply that HMGA proteins also act in tumor suppressor networks. ..
- Cavazzana Calvo M, Payen E, Negre O, Wang G, Hehir K, Fusil F, et al. Transfusion independence and HMGA2 activation after gene therapy of human ?-thalassaemia. Nature. 2010;467:318-22 pubmed publisher..The clonal dominance that accompanies therapeutic efficacy may be coincidental and stochastic or result from a hitherto benign cell expansion caused by dysregulation of the HMGA2 gene in stem/progenitor cells. ..
- Andrieux J, Demory J, Dupriez B, Quief S, Plantier I, Roumier C, et al. Dysregulation and overexpression of HMGA2 in myelofibrosis with myeloid metaplasia. Genes Chromosomes Cancer. 2004;39:82-7 pubmed..We postulate that its dysregulation and overexpression in myeloid progenitors contribute also to the pathogenesis of MMM. ..
- Sun T, Fu M, Bookout A, Kliewer S, Mangelsdorf D. MicroRNA let-7 regulates 3T3-L1 adipogenesis. Mol Endocrinol. 2009;23:925-31 pubmed publisher..These results suggest that let-7 plays an important role in adipocyte differentiation and that it does so in part by targeting HMGA2, thereby regulating the transition from clonal expansion to terminal differentiation. ..
- Copley M, Babovic S, Benz C, Knapp D, Beer P, Kent D, et al. The Lin28b-let-7-Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells. Nat Cell Biol. 2013;15:916-25 pubmed publisher..Thus, Lin28b may act as a master regulator of developmentally timed changes in HSC programs with Hmga2 serving as its specific downstream modulator of HSC self-renewal potential. ..
- Funayama R, Saito M, Tanobe H, Ishikawa F. Loss of linker histone H1 in cellular senescence. J Cell Biol. 2006;175:869-80 pubmed..001). It is known that histone H1 and HMG proteins compete for a common binding site, the linker DNA. These results suggest that SAHFs are a novel type of chromatin condensation involving alterations in linker DNA-binding proteins. ..
- Zaidi M, Okada Y, Chada K. Misexpression of full-length HMGA2 induces benign mesenchymal tumors in mice. Cancer Res. 2006;66:7453-9 pubmed
- Cattaruzzi G, Altamura S, Tessari M, Rustighi A, Giancotti V, Pucillo C, et al. The second AT-hook of the architectural transcription factor HMGA2 is determinant for nuclear localization and function. Nucleic Acids Res. 2007;35:1751-60 pubmed..HMGA proteins are overexpressed and rearranged in a variety of tumors; our findings can thus help elucidating their role in neoplastic transformation. ..
- Peng Y, Laser J, Shi G, Mittal K, Melamed J, Lee P, et al. Antiproliferative effects by Let-7 repression of high-mobility group A2 in uterine leiomyoma. Mol Cancer Res. 2008;6:663-73 pubmed publisher..Our findings suggest that the Let-7-mediated repression of HMGA2 mechanism can be an important molecular event in leiomyoma growth. ..
- Dahlén A, Mertens F, Rydholm A, Brosjo O, Wejde J, Mandahl N, et al. Fusion, disruption, and expression of HMGA2 in bone and soft tissue chondromas. Mod Pathol. 2003;16:1132-40 pubmed..A truncated or full-length transcript was found in 8 of 13 chondrosarcomas, 4 of which displayed 12q rearrangements. Possibly, cryptic rearrangements were present among the many complex marker chromosomes in the remaining 4 cases. ..
- Pentimalli F, Dentice M, Fedele M, Pierantoni G, Cito L, Pallante P, et al. Suppression of HMGA2 protein synthesis could be a tool for the therapy of well differentiated liposarcomas overexpressing HMGA2. Cancer Res. 2003;63:7423-7 pubmed..an adenovirus containing the HMGA2 gene in the antisense orientation (Ad-A2as) to study the effect of HMGA2 protein suppression in ALT cells...
- Ashar H, Fejzo M, Tkachenko A, Zhou X, Fletcher J, Weremowicz S, et al. Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains. Cell. 1995;82:57-65 pubmed..These results, identifying a gene rearranged in a benign neoplastic process that does not proceed to a malignancy, suggest a role for HMGI-C in adipogenesis and mesenchyme differentiation. ..
- Cleynen I, Brants J, Peeters K, Deckers R, Debiec Rychter M, Sciot R, et al. HMGA2 regulates transcription of the Imp2 gene via an intronic regulatory element in cooperation with nuclear factor-kappaB. Mol Cancer Res. 2007;5:363-72 pubmed..Finally, we provide evidence that there is a strong and statistically significant correlation between HMGA2 and IMP2 gene expression in human liposarcomas. ..
- Bartuma H, Hallor K, Panagopoulos I, Collin A, Rydholm A, Gustafson P, et al. Assessment of the clinical and molecular impact of different cytogenetic subgroups in a series of 272 lipomas with abnormal karyotype. Genes Chromosomes Cancer. 2007;46:594-606 pubmed..By FISH, we could also show that breakpoints in bands 10q22-23 do not affect the MYST4 gene, whereas breakpoints in 6p21 or 8q11-12 occasionally target the HMGA1 or PLAG1 genes, respectively, also in conventional lipomas. ..
- Li Z, Zhang Y, Ramanujan K, Ma Y, Kirsch D, Glass D. Oncogenic NRAS, required for pathogenesis of embryonic rhabdomyosarcoma, relies upon the HMGA2-IGF2BP2 pathway. Cancer Res. 2013;73:3041-50 pubmed publisher..Taken together, these findings implicate the HMGA2-IGFBP2-NRAS signaling pathway as a critical oncogenic driver in ERMS. ..
- Borrmann L, Schwanbeck R, Heyduk T, Seebeck B, Rogalla P, Bullerdiek J, et al. High mobility group A2 protein and its derivatives bind a specific region of the promoter of DNA repair gene ERCC1 and modulate its activity. Nucleic Acids Res. 2003;31:6841-51 pubmed..Our results provide the first insights into how HMGA2 and its aberrant forms bind and regulate the ERCC1 promoter. ..
- Chau K, Manfioletti G, Cheung Chau K, Fusco A, Dhomen N, Sowden J, et al. Derepression of HMGA2 gene expression in retinoblastoma is associated with cell proliferation. Mol Med. 2003;9:154-65 pubmed..Our discovery of derepression of HMGA2 gene expression in retinoblastoma provides the 1st evidence that this protein might contribute to neoplastic transformation of retina cells. ..
- Schoenmakers E, Wanschura S, Mols R, Bullerdiek J, Van den Berghe H, Van de Ven W. Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours. Nat Genet. 1995;10:436-44 pubmed..These results suggest a link between a member of the HMG gene family and benign solid tumour development. ..
- Vallone D, Battista S, Pierantoni G, Fedele M, Casalino L, Santoro M, et al. Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product. EMBO J. 1997;16:5310-21 pubmed
- Shell S, Park S, Radjabi A, Schickel R, Kistner E, Jewell D, et al. Let-7 expression defines two differentiation stages of cancer. Proc Natl Acad Sci U S A. 2007;104:11400-5 pubmed..These data identify loss of let-7 expression as a marker for less differentiated cancer. ..
- Yu K, Park S, Jung J, Seo M, Hong I, Kim H, et al. HMGA2 regulates the in vitro aging and proliferation of human umbilical cord blood-derived stromal cells through the mTOR/p70S6K signaling pathway. Stem Cell Res. 2013;10:156-65 pubmed publisher..These results provide novel insights into the mechanism by which HMGA2 regulates the in vitro aging and proliferation of hUCBSCs. ..