HMGA2 Expression in Cancer Metastasis and Progression

High mobility group A2 (HMGA2) is a non-histone chromatin-binding protein that is abundant during embryogenesis but largely silenced in differentiated adult tissues. In many malignancies HMGA2 is re-expressed and acts as a central orchestrator of oncogenic programmes. By altering chromatin architecture at AT-rich sequences, HMGA2 modulates gene transcription and enhances pathways governing cell cycle entry, evasion of apoptosis and DNA damage repair. Critically, HMGA2 drives epithelial-to-mesenchymal transition (EMT) through activation of TGFβ/Smad, Wnt/β-catenin, PI3K/Akt/mTOR and MAPK/ERK cascades, fostering migratory and invasive phenotypes. It also sustains a cancer stem-like state, conferring resistance to chemotherapy and radiotherapy. Clinically, elevated HMGA2 correlates with advanced tumour stage, lymph node involvement and distant metastasis across diverse carcinoma types, underscoring its prognostic value. Therapeutic strategies under exploration include targeting HMGA2 expression with non-coding RNAs, disrupting key protein interactions and modulating upstream epigenetic regulators to curb metastatic dissemination.

Research from Nature Portfolio

MicroRNA-33b has been identified as a potent suppressor of breast cancer metastasis through direct targeting of HMGA2 alongside other transcriptional regulators. Restoration of miR-33b in highly metastatic breast cancer cells significantly attenuates cell migration, invasion and stemness in vitro and reduces lung colonisation in vivo. These findings establish a foundational link between a specific microRNA and HMGA2-driven metastatic programmes, highlighting the therapeutic promise of microRNA replacement to inhibit HMGA2-mediated cancer progression.

HMGA2 Expression in Cancer Metastasis and Progression publication trend

The graph below shows the total number of articles in hmga2 expression in cancer metastasis and progression across all publications each year (not limited to Nature Index journals).

Technical terms

HMGA2: A chromatin-binding protein with AT-hook motifs that alters DNA conformation and regulates transcription.

Epithelial-to-Mesenchymal Transition (EMT): A cellular programme during which epithelial cells acquire mesenchymal traits, enhancing motility and invasiveness.

MicroRNA (miRNA): Small non-coding RNA molecules that bind complementary mRNA sequences to inhibit translation or promote degradation.

Chromatin Remodelling: Dynamic modification of chromatin structure by specialised proteins to regulate gene accessibility and expression.

Epigenetic Silencing: Repression of gene expression through DNA methylation or histone modifications without altering the DNA sequence.

References

1. HMGA2 as a Critical Regulator in Cancer Development. Genes (2021).
2. HMGA proteins as modulators of chromatin structure during transcriptional activation. Frontiers in Cell and Developmental Biology (2014).
3. MicroRNA-33b Inhibits Breast Cancer Metastasis by Targeting HMGA2, SALL4 and Twist1. Scientific Reports (2015).
4. Nuclear High Mobility Group A2 (HMGA2) Interactome Revealed by Biotin Proximity Labeling. International Journal of Molecular Sciences (2023).
5. EZH2-mediated epigenetic silencing of tumor-suppressive let-7c/miR-99a cluster by hepatitis B virus X antigen enhances hepatocellular carcinoma progression and metastasis. Cancer Cell International (2023).
6. HMGA2 regulation by miRNAs in cancer: Affecting cancer hallmarks and therapy response. Pharmacological Research (2023).
7. miR-302a-5p/367-3p-HMGA2 axis regulates malignant processes during endometrial cancer development. Journal of Experimental & Clinical Cancer Research (2018).