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Gene Review

HMGA2  -  high mobility group AT-hook 2

Homo sapiens

Synonyms: BABL, HMGI-C, HMGIC, High mobility group AT-hook protein 2, High mobility group protein HMGI-C, ...
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Disease relevance of HMGA2


Psychiatry related information on HMGA2

  • We also observed that blood adipsin concentrations can vary as a function of feeding or adiposity, in that they tend to be mildly elevated in obese individuals or mildly reduced in individuals with total lipo-atrophy, cachexia related to AIDS and anorexia nervosa [7].

High impact information on HMGA2


Chemical compound and disease context of HMGA2


Biological context of HMGA2


Anatomical context of HMGA2

  • No structural alterations were observed at the HMGA2 locus in either primary rat leiomyomas or leiomyoma-derived cell lines that expressed HMGA2 [1].
  • These data support a role for HMGA2 in the development of smooth muscle neoplasms and suggest HMGA2 expression is a point of convergence between the human disease and the Eker rat model [1].
  • HMGA2 is expressed only in a subset of ex vivo neuroblastoma (NB) tumors and in the embryonic adrenal gland, but it is undetectable in the adult adrenal gland, suggesting that its anomalous expression might be associated with NB tumorigenesis and/or tumor progression [19].
  • The lipoma preferred partner (LPP) gene is the most frequent translocation partner of HMGA2 in a subgroup of lipomas, which are benign tumors of adipose tissue [20].
  • HMGA2 is an architectural transcriptional factor that is expressed in the undifferentiated mesenchyme and initiates mesenchymal tumor formation [21].

Associations of HMGA2 with chemical compounds

  • The HMGA2 protein belongs to the HMGA family of architectural transcription factors, which play an important role in chromatin organization [16].
  • These findings should contribute to a greater understanding of the role of HMGA2 in promoting tumorigenesis and conveying (chemo)sensitivity towards doxorubicin and other related double-strand breaks [12].
  • Moreover, this HMGA2-dependent enhancement of cytotoxicity is further extended to other double-strand breaks elicited by cisplatin and X-ray irradiation and is not restricted to one cell type [12].
  • Notably, HMGA2 enhances doxorubicin-elicited cell cycle delay in sub-G1 and G2-M and augments cell cycle dysregulation on cotreatment of doxorubicin and caffeine [12].
  • We then evaluated the expression of the PPARalpha, PPARgamma2, HMGA2, leptin and TSHr genes before and after 24 h of fenofibrate treatment, using semiquantitative and real-time PCR [22].

Physical interactions of HMGA2

  • Our results provide the first insights into how HMGA2 and its aberrant forms bind and regulate the ERCC1 promoter [23].
  • These transcripts encode fusion proteins containing RAD51L1 nucleotide binding domains and the HMGIC protein lacking the N-terminal AT hook motifs [24].

Regulatory relationships of HMGA2

  • To check if HMGA expression is under control of such elements we performed luciferase assays with several HMGA2 and HMGA1 3'UTRs of different length [25].
  • Furthermore, the regulatory effect of HMGA2 was confirmed by luciferase promoter assays showing that ERCC1 promoter activity is down-regulated by all investigated HMGA2 forms, with the most striking effect exerted by DeltaHMGA2 [23].
  • In normal salivary gland tissue WIF1 is expressed at a high level and HMGA2 is not expressed [26].

Other interactions of HMGA2

  • RAD51L1-HMGA2 transcripts were not detected [17].
  • Experiments showed that an up to 12-fold increase in luciferase activity is obtained by the truncation of the 3'UTRs suggesting that the expression of HMGA2 and HMGA1 is controlled by negatively acting regulatory elements within their 3'UTR [25].
  • In addition, chromatin immunoprecipitation experiments show that HMGA2 associates with the cyclin A promoter only when the gene is transcriptionally activated [16].
  • Overexpression of HMGA2-LPP fusion transcripts promotes expression of the alpha 2 type XI collagen gene [27].
  • Differential expression of HMGA1 and HMGA2 in dermatofibroma and dermatofibrosarcoma protuberans: potential diagnostic applications, and comparison with histologic findings, CD34, and factor XIIIa immunoreactivity [28].

Analytical, diagnostic and therapeutic context of HMGA2


  1. Aberrant expression of HMGA2 in uterine leiomyoma associated with loss of TSC2 tumor suppressor gene function. Hunter, D.S., Klotzbücher, M., Kugoh, H., Cai, S.L., Mullen, J.P., Manfioletti, G., Fuhrman, U., Walker, C.L. Cancer Res. (2002) [Pubmed]
  2. Increased expression of high mobility group A proteins in lung cancer. Sarhadi, V.K., Wikman, H., Salmenkivi, K., Kuosma, E., Sioris, T., Salo, J., Karjalainen, A., Knuutila, S., Anttila, S. J. Pathol. (2006) [Pubmed]
  3. Repression of HMGA2 Gene Expression by Human Cytomegalovirus Involves the IE2 86-Kilodalton Protein and Is Necessary for Efficient Viral Replication and Inhibition of Cyclin A Transcription. Shlapobersky, M., Sanders, R., Clark, C., Spector, D.H. J. Virol. (2006) [Pubmed]
  4. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Lee, Y.S., Dutta, A. Genes Dev. (2007) [Pubmed]
  5. Identification of the benign mesenchymal tumor gene HMGA2 in lymphangiomyomatosis. D'Armiento, J., Imai, K., Schiltz, J., Kolesnekova, N., Sternberg, D., Benson, K., Pardo, A., Selman, M., Smolarek, T., Vundavalli, M., Sonnet, J., Szabolcs, M., Chada, K. Cancer Res. (2007) [Pubmed]
  6. Overexpression of HMGA2 Promotes Metastasis and Impacts Survival of Colorectal Cancers. Wang, X., Liu, X., Li, A.Y., Chen, L., Lai, L., Lin, H.H., Hu, S., Yao, L., Peng, J., Loera, S., Xue, L., Zhou, B., Zhou, L., Zheng, S., Chu, P., Zhang, S., Ann, D.K., Yen, Y. Clin. Cancer Res. (2011) [Pubmed]
  7. Concentrations of adipsin in blood and rates of adipsin secretion by adipose tissue in humans with normal, elevated and diminished adipose tissue mass. Napolitano, A., Lowell, B.B., Damm, D., Leibel, R.L., Ravussin, E., Jimerson, D.C., Lesem, M.D., Van Dyke, D.C., Daly, P.A., Chatis, P. Int. J. Obes. Relat. Metab. Disord. (1994) [Pubmed]
  8. A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Narita, M., Narita, M., Krizhanovsky, V., Nuñez, S., Chicas, A., Hearn, S.A., Myers, M.P., Lowe, S.W. Cell (2006) [Pubmed]
  9. Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours. Schoenmakers, E.F., Wanschura, S., Mols, R., Bullerdiek, J., Van den Berghe, H., Van de Ven, W.J. Nat. Genet. (1995) [Pubmed]
  10. Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains. Ashar, H.R., Fejzo, M.S., Tkachenko, A., Zhou, X., Fletcher, J.A., Weremowicz, S., Morton, C.C., Chada, K. Cell (1995) [Pubmed]
  11. HMGA proteins in malignant peripheral nerve sheath tumor and synovial sarcoma: preferential expression of HMGA2 in malignant peripheral nerve sheath tumor. Hui, P., Li, N., Johnson, C., De Wever, I., Sciot, R., Manfioletti, G., Tallini, G. Mod. Pathol. (2005) [Pubmed]
  12. High mobility group A2 potentiates genotoxic stress in part through the modulation of basal and DNA damage-dependent phosphatidylinositol 3-kinase-related protein kinase activation. Boo, L.M., Lin, H.H., Chung, V., Zhou, B., Louie, S.G., O'Reilly, M.A., Yen, Y., Ann, D.K. Cancer Res. (2005) [Pubmed]
  13. Expression profile of the tumorigenic factors associated with tumor size and sex steroid hormone status in uterine leiomyomata. Wei, J.J., Chiriboga, L., Mittal, K. Fertil. Steril. (2005) [Pubmed]
  14. Genomic changes in endometrial polyps associated with tamoxifen show no evidence for its action as an external carcinogen. Dal Cin, P., Timmerman, D., Van den Berghe, I., Wanschura, S., Kazmierczak, B., Vergote, I., Deprest, J., Neven, P., Moerman, P., Bullerdiek, J., Van den Berghe, H. Cancer Res. (1998) [Pubmed]
  15. HMGI(Y) and HMGI-C genes are expressed in neuroblastoma cell lines and tumors and affect retinoic acid responsiveness. Giannini, G., Di Marcotullio, L., Ristori, E., Zani, M., Crescenzi, M., Scarpa, S., Piaggio, G., Vacca, A., Peverali, F.A., Diana, F., Screpanti, I., Frati, L., Gulino, A. Cancer Res. (1999) [Pubmed]
  16. Transcriptional activation of the cyclin A gene by the architectural transcription factor HMGA2. Tessari, M.A., Gostissa, M., Altamura, S., Sgarra, R., Rustighi, A., Salvagno, C., Caretti, G., Imbriano, C., Mantovani, R., Del Sal, G., Giancotti, V., Manfioletti, G. Mol. Cell. Biol. (2003) [Pubmed]
  17. Fusion transcripts involving HMGA2 are not a common molecular mechanism in uterine leiomyomata with rearrangements in 12q15. Quade, B.J., Weremowicz, S., Neskey, D.M., Vanni, R., Ladd, C., Dal Cin, P., Morton, C.C. Cancer Res. (2003) [Pubmed]
  18. Human HMGA2 promoter is coregulated by a polymorphic dinucleotide (TC)-repeat. Borrmann, L., Seebeck, B., Rogalla, P., Bullerdiek, J. Oncogene (2003) [Pubmed]
  19. HMGA molecules in neuroblastic tumors. Cerignoli, F., Ambrosi, C., Mellone, M., Assimi, I., di Marcotullio, L., Gulino, A., Giannini, G. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  20. Transactivation functions of the tumor-specific HMGA2/LPP fusion protein are augmented by wild-type HMGA2. Crombez, K.R., Vanoirbeek, E.M., Van de Ven, W.J., Petit, M.M. Mol. Cancer Res. (2005) [Pubmed]
  21. Expression of mesenchyme-specific gene HMGA2 in squamous cell carcinomas of the oral cavity. Miyazawa, J., Mitoro, A., Kawashiri, S., Chada, K.K., Imai, K. Cancer Res. (2004) [Pubmed]
  22. Fenofibrate increases the expression of high mobility group AT-hook 2 (HMGA2) gene and induces adipocyte differentiation of orbital fibroblasts from Graves' ophthalmopathy. Pasquali, D., Pierantoni, G.M., Fusco, A., Staibano, S., Colantuoni, V., De Bellis, A., Bellastella, A., Sinisi, A.A. J. Mol. Endocrinol. (2004) [Pubmed]
  23. High mobility group A2 protein and its derivatives bind a specific region of the promoter of DNA repair gene ERCC1 and modulate its activity. Borrmann, L., Schwanbeck, R., Heyduk, T., Seebeck, B., Rogalla, P., Bullerdiek, J., Wisniewski, J.R. Nucleic Acids Res. (2003) [Pubmed]
  24. Evidence for RAD51L1/HMGIC fusion in the pathogenesis of uterine leiomyoma. Takahashi, T., Nagai, N., Oda, H., Ohama, K., Kamada, N., Miyagawa, K. Genes Chromosomes Cancer (2001) [Pubmed]
  25. The expression of HMGA genes is regulated by their 3'UTR. Borrmann, L., Wilkening, S., Bullerdiek, J. Oncogene (2001) [Pubmed]
  26. WIF1, an inhibitor of the Wnt pathway, is rearranged in salivary gland tumors. Queimado, L., Lopes, C.S., Reis, A.M. Genes Chromosomes Cancer (2007) [Pubmed]
  27. Overexpression of HMGA2-LPP fusion transcripts promotes expression of the alpha 2 type XI collagen gene. Kubo, T., Matsui, Y., Goto, T., Yukata, K., Yasui, N. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  28. Differential expression of HMGA1 and HMGA2 in dermatofibroma and dermatofibrosarcoma protuberans: potential diagnostic applications, and comparison with histologic findings, CD34, and factor XIIIa immunoreactivity. Li, N., McNiff, J., Hui, P., Manfioletti, G., Tallini, G. The American Journal of dermatopathology. (2004) [Pubmed]
  29. Molecular dissection of the architectural transcription factor HMGA2. Noro, B., Licheri, B., Sgarra, R., Rustighi, A., Tessari, M.A., Chau, K.Y., Ono, S.J., Giancotti, V., Manfioletti, G. Biochemistry (2003) [Pubmed]
  30. The High Mobility Group A2 gene is amplified and overexpressed in human prolactinomas. Finelli, P., Pierantoni, G.M., Giardino, D., Losa, M., Rodeschini, O., Fedele, M., Valtorta, E., Mortini, P., Croce, C.M., Larizza, L., Fusco, A. Cancer Res. (2002) [Pubmed]
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