The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development
Year: 2016
Type: article
Abstract: BACKGROUND & OBJECTIVES: 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. CONCLUSION: Further elucidation of HMGA1 function should lead to novel therapeutic strategies for cancer and possibly for other diseases associated with aberrant HMGA1 expression.
Source: Current Molecular Medicine
Authors: T.F. Sumter, L. Xian, T. Huso, M. Koo, Y.-T. Chang, T.N. Almasri, L. Chia, C. Inglis, D. Reid, L.M.S. Resar
Institutions: Johns Hopkins University, Johns Hopkins Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Structure Function Studies of the HMGA1 Functional Domains Involved in Malignant , South Carolina IDeA Network of Biomedical Research Excellence, Developing Nanotechnology to Target HMGA1 in Pancreatic Cancer, HMGA1 in Tumor Progression in Breast Cancer, Prevention of COX-2 Derived DNA and Histone Modifications in Cancer, The Role of HMG-I/Y in Uterine Cancer, G4990271298, G529529811, Developing a Screen for Novel Therapies with Reprogrammed Pancreatic Cancer Cells, Mechanisms of Neoplastic Transformation by HMG-I/Y, Targeting HMGA1 in Pancreatic Tumor Progression, South Carolina IDeA Networks of Biomedical Research Excellence (SC INBRE), Targeting the let-7-HMGA2 Network in Metastatic Progression in Pancreatic Cancer
OpenAlex ID: W2299167488