HMGA1 (High Mobility Group AT-Hook 1)

This review summarizes the cellular and molecular functions of HMGA1 in regulating genomic integrity and cell death in cancer. Furthermore, we discuss current HMGA1-targeting strategies, with emphasis on approaches leveraging its structural and functional characteristics, aiming to provide new insights for future research on HMGA1-targeted cancer therapies.

The risk model constructed in this study effectively predicts the prognosis of LUAD patients. PLEK2 is highly expressed in LUAD and associated with EGFR-TKIs resistance, suggesting its potential as a prognostic biomarker and therapeutic target.

Drug sensitivity analysis further revealed that HMGA1 predicted resistance to AKT inhibitors, which was experimentally validated in breast cancer cells treated with Capivasertib. Collectively, our findings establish HMGA1 as a pivotal oncogenic regulator and a promising biomarker for prognosis and for guiding strategies in immunotherapy and overcoming targeted therapy resistance.

HMGA1 protein levels decreased in the range of 40, 50 and 70% with shRNA, AAT and HBS viruses, respectively. The HBS virus designed to sequester HMGA1 proved most effective overall in suppressing HMGA1 oncogenic activity in these in vitro cell-based studies compared to the AAT and shRNA viruses.

Here, we have characterized the genomic landscape of endometrial polyps. We show that chromosomal alterations affecting HMGA1 and HMGA2 are a major underlying cause for polyp development. In addition, we present UBE2A as a novel candidate gene for human tumorigenesis. Our results contribute to a better understanding of endometrial polyp development and pave the way towards the development of targeted, non-invasive treatment options.

Further analyses identified HMGA1 as a core gene within the model, closely linked to adverse outcomes; functional assays demonstrated that high HMGA1 expression promotes the proliferation and migration of the LLC cell line, supporting its role in metastatic progression. Collectively, this study defines the immune microenvironmental remodelling associated with lymph node metastasis, establishes an effective risk prediction model (LNRScore), and highlights HMGA1 as a potential target for precision diagnosis and therapy in lung adenocarcinoma.

In addition, CN-3 could upregulate the expression of miR-4465 in cells, thereby inhibiting migration and invasion of glioma cells. These results elucidate the mechanism by which CN-3, a steroidal saponin from the sea, may inhibit the invasive behavior of glioma cells through the miRNA-4465/HMGA1/NF-κB pathway, which also raise the prospect of using CN-3 as a chemotherapeutic agent to prevent glioma invasive growth.

Upstream analysis showed that cg25207224HMGA1 tested by oral rinse specimen maybe a non-invasive in-vitro predictive marker for prognostic prediction of HNSCC. Our study revealed the impact of HMGA1 on tumorigenesis, prognosis and immune microenvironment in HNSCC from a multi-omics perspective and provided a therapeutic target for HNSCC patients.

Finally, we confirmed in vivo that PTE treatment reduced the expression of HMGA1/2 and Snai1/2 (markers of EndMT), and restored the expression of von Willebrand factor in the lungs of PAH rats. PTE mitigates MCT-induced PAH and vascular remodeling in rats, at least in part, by inhibiting HMGA-mediated EndMT, suggesting that PTE may be a useful complementary medicine in the treatment of PAH.

Additionally, we design and synthesize a series of HMGA1 inhibitors, including a perylene-based nanoparticle, PDIC-DPC, which effectively inhibits HMGA1 and enhances TIL infiltration. Our findings identify HMGA1 as a critical immune checkpoint in ESCC and suggest that targeting HMGA1 could improve immunotherapy outcomes.

M2-TAM-isolated CCL18 facilitated EC progression by activating the TWIST1/HMGA1 axis. These observations might offer new directions for developing targeted curative interventions for EC.