ArticleActa pharmaceutica Sinica. B2024
Blockade of the deubiquitinating enzyme USP48 degrades oncogenic HMGA2 and inhibits colorectal cancer invasion and metastasis.
Article in Acta pharmaceutica Sinica. B, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 15 citations in OpenAlex.
- METTL1/USP48 Axis Stabilizes LCN2 Expression to Promote the Malignant Phenotypes of Cutaneous Squamous Cell Carcinoma.Applied biochemistry and biotechnology · 2026Article
- Targeting USP8 with odoroside A regulates LXRβ-mediated fatty acid metabolic reprogramming against colorectal cancer.Acta pharmacologica Sinica · 2026Article
- Deubiquitinase USP48 Promotes Gastric Cancer Peritoneal Metastasis by Stabilizing S100A9 to Drive Neutrophil Extracellular Traps Formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Ubiquitin Specific Peptidase 48 Deubiquitinates METTL3 to Modulate Ferroptosis in Gastric Cancer Cells.Molecular carcinogenesis · 2026Article
- USP48 functions as a suppressor of colorectal cancer via SELENBP1 stabilization.Translational oncology · 2026Article
- EIF3H Modulates Glycolysis Through LDHA Stabilization in Triple-Negative Breast Cancer.Cancers · 2026Article
- Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML.Cancer biology & therapy · 2025Article
- Ubiquitin-specific proteases as key regulators in the malignant progression and therapy resistance of colorectal cancer: current insights and future perspectives.Discover oncology · 2025Review
- Integrative analysis identifies LHFPL6 as a CAF-specific prognostic biomarker in colorectal cancer.Clinical and experimental medicine · 2025Article
- Review
- USP39 promote post-translational modifiers to stimulate the progress of cancer.Discover oncology · 2025Review
- CDK1-mediated phosphorylation of USP37 regulates SND1 stability and promotes oncogenesis in colorectal cancer.Acta pharmaceutica Sinica. B · 2025Article
- Hexokinase 2 Suppression Alleviates the Catabolic Properties in Osteoarthritis via HMGA2 and Contributes to Pulsed Electromagnetic Field-mediated Cartilage Protection.International journal of biological sciences · 2025Article
- UBE2G2 inhibits vasculogenic mimicry and metastasis of uveal melanoma by promoting ubiquitination of LGALS3BP.Acta pharmaceutica Sinica. B · 2024Article
- A phosphoglycerate mutase 1 allosteric inhibitor restrains TAM-mediated colon cancer progression.Acta pharmaceutica Sinica. B · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HMGA2, a pivotal transcription factor, functions as a versatile regulator implicated in the progression of diverse aggressive malignancies. In this study, mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2, and USP48 was identified as a deubiquitinating enzyme of HMGA2. The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation, while the deprivation of USP48 promoted HMGA2 degradation, thereby suppressing tumor invasion and metastasis. We discovered that USP48 undergoes SUMOylation at lysine 258, which enhances its binding affinity to HMGA2. Through subsequent phenotypic screening of small molecules, we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48. Interestingly, the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2. Clinically, upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer (CRC). Collectively, our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC, but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.