title: The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development.
abstract: OBJECTIVE
  Chromatin structure is the single most important feature that distinguishes a cancer cell from a normal cell histologically. Chromatin remodeling proteins regulate chromatin structure and high mobility group A (HMGA1) proteins are among the most abundant, nonhistone chromatin remodeling proteins found in cancer cells. These proteins include HMGA1a/HMGA1b isoforms, which result from alternatively spliced mRNA. The HMGA1 gene is overexpressed in cancer and high levels portend a poor prognosis in diverse tumors. HMGA1 is also highly expressed during embryogenesis and postnatally in adult stem cells. Overexpression of HMGA1 drives neoplastic transformation in cultured cells, while inhibiting HMGA1 blocks oncogenic and cancer stem cell properties. Hmga1 transgenic mice succumb to aggressive tumors, demonstrating that dysregulated expression of HMGA1 causes cancer in vivo. HMGA1 is also required for reprogramming somatic cells into induced pluripotent stem cells. HMGA1 proteins function as ancillary transcription factors that bend chromatin and recruit other transcription factors to DNA. They induce oncogenic transformation by activating or repressing specific genes involved in this process and an HMGA1 "transcriptome" is emerging. Although prior studies reveal potent oncogenic properties of HMGA1, we are only beginning to understand the molecular mechanisms through which HMGA1 functions. In this review, we summarize the list of putative downstream transcriptional targets regulated by HMGA1. We also briefly discuss studies linking HMGA1 to Alzheimer's disease and type-2 diabetes.
  
  
  CONCLUSIONS
  Further elucidation of HMGA1 function should lead to novel therapeutic strategies for cancer and possibly for other diseases associated with aberrant HMGA1 expression.
authors.forename: T F
authors.initials: TF
authors.lastname: Sumter
authors.forename: L
authors.initials: L
authors.lastname: Xian
authors.forename: T
authors.initials: T
authors.lastname: Huso
authors.forename: M
authors.initials: M
authors.lastname: Koo
authors.forename: Y-T
authors.initials: YT
authors.lastname: Chang
authors.forename: T N
authors.initials: TN
authors.lastname: Almasri
authors.forename: L
authors.initials: L
authors.lastname: Chia
authors.forename: C
authors.initials: C
authors.lastname: Inglis
authors.forename: D
authors.initials: D
authors.lastname: Reid
authors.affiliation: Department of Medicine, Faculty of the Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Room 1025, Baltimore, MD 21205-2109, USA. lresar@jhmi.edu.
authors.forename: L M S
authors.initials: LM
authors.lastname: Resar
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D048788:Growth and Development / Q000235:genetics*; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D039904:Pluripotent Stem Cells / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics*
chemical_list: D025741:HMGA1a Protein