The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development

Overview

Journal Curr Mol Med

Publisher Bentham Science Publishers

Specialty Molecular Biology

Date 2016 Mar 17

PMID 26980699

Citations 67

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

Affiliations

Soon will be listed here.

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.

Citing Articles

High Mobility Group A1 Chromatin Keys: Unlocking the Genome During MPN Progression.

Resar L, Luo L Int J Mol Sci. 2025; 26(5).

PMID: 40076747 PMC: 11899949. DOI: 10.3390/ijms26052125.

HMGA1 acts as an epigenetic gatekeeper of ASCL2 and Wnt signaling during colon tumorigenesis.

Luo L, Kim J, Herrera I, Wu S, Wu X, Park S J Clin Invest. 2025; 135(3).

PMID: 39895630 PMC: 11785931. DOI: 10.1172/JCI184442.

A Murine Database of Structural Variants Enables the Genetic Architecture of a Spontaneous Murine Lymphoma to be Characterized.

Ren W, Fang Z, Dolzhenko E, Saunders C, Cheng Z, Popic V bioRxiv. 2025; .

PMID: 39868308 PMC: 11761040. DOI: 10.1101/2025.01.09.632219.

HMGA1 Regulates IRS2 to Promote Inflammatory Responses and Oxidative Stress Injury in MPP-Induced cells.

Xu D, Fan W, Fu B, Nie H Cell Biochem Biophys. 2024; 83(1):783-792.

PMID: 39244689 DOI: 10.1007/s12013-024-01510-7.

Binding to the Other Side: The AT-Hook DNA-Binding Domain Allows Nuclear Factors to Exploit the DNA Minor Groove.

Battista S, Fedele M, Secco L, Ingo A, Sgarra R, Manfioletti G Int J Mol Sci. 2024; 25(16).

PMID: 39201549 PMC: 11354804. DOI: 10.3390/ijms25168863.

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