ArticleMolecular and cellular biology2011
High-mobility group A2 protein modulates hTERT transcription to promote tumorigenesis.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- Review
- HMGA2 promotes nasopharyngeal carcinoma progression and is associated with tumor resistance and poor prognosis.Frontiers in oncology · 2023Review
- Downregulation of HMGA2 by Small Interfering RNA Affects the Survival, Migration, and Apoptosis of Prostate Cancer Cell Line.Advanced pharmaceutical bulletin · 2022Article
- The regulation of acetylation and stability of HMGA2 via the HBXIP-activated Akt-PCAF pathway in promotion of esophageal squamous cell carcinoma growth.Nucleic acids research · 2020Article
- Metformin alleviates breast cancer through targeting high-mobility group AT-hook 2.Thoracic cancer · 2020Article
- Alterations in TGF-β signaling leads to high HMGA2 levels potentially through modulation of PJA1/SMAD3 in HCC cells.Genes & cancer · 2020Article
- Identification of differential gene expression in endothelial cells from young and aged mice using RNA-Seq technique.American journal of translational research · 2019Article
- The Linker Histone GH1-HMGA1 Is Involved in Telomere Stability and DNA Damage Repair.Plant physiology · 2018Article
- High mobility group protein A2 overexpression indicates poor prognosis for cancer patients: a meta-analysis.Oncotarget · 2018Article
- Telomere shortening in breast cancer cells (MCF7) under treatment with low doses of the benzylisoquinoline alkaloid chelidonine.PloS one · 2018Article
- Review
- Sister chromatid telomere fusions, but not NHEJ-mediated inter-chromosomal telomere fusions, occur independently of DNA ligases 3 and 4.Genome research · 2016Article
- Telomerase activity in breast cancer patients: association with poor prognosis and more aggressive phenotype.Medical oncology (Northwood, London, England) · 2016Article
- A novel anti-proliferative role of HMGA2 in induction of apoptosis through caspase 2 in primary human fibroblast cells.Bioscience reports · 2015Article
- Telomerase downregulation induces proapoptotic genes expression and initializes breast cancer cells apoptosis followed by DNA fragmentation in a cell type dependent manner.Molecular biology reports · 2013Article
- Probing into the biological processes influenced by ESC factor and oncoprotein HMGA2 using iPSCs.Stem cell reviews and reports · 2013Article
- Telomerase as a useful target in cancer fighting-the breast cancer case.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Review
- Oncogenic NRAS, required for pathogenesis of embryonic rhabdomyosarcoma, relies upon the HMGA2-IGF2BP2 pathway.Cancer research · 2013Article
- HMGA2 induces epithelial-to-mesenchymal transition in human hepatocellular carcinoma cells.Oncology letters · 2013Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
The high-mobility group A2 gene (HMGA2) is one of the most frequently amplified genes in human cancers. However, functions of HMGA2 in tumorigenesis are not fully understood due to limited knowledge of its targets in tumor cells. Our study reveals a novel link between HMGA2 and the regulation of human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, which offers critical insight into how HMGA2 contributes to tumorigenesis. The expression of HMGA2 modulates the expression of hTERT, resulting in cells with enhanced telomerase activities and increased telomere length. Treatment with suberoylanilide hydroxamide (SAHA), a histone deacetylase (HDAC) inhibitor, causes dose-dependent hTERT reporter activation, mimicking HMGA2 overexpression. By interacting with Sp1, HMGA2 interferes with the recruitment of HDAC2 to the hTERT proximal promoter, enhancing localized histone H3-K9 acetylation and thereby stimulating hTERT expression and telomerase activity. Moreover, HMGA2 knockdown by short hairpin HMGA2 in HepG2 cells leads to progressive telomere shortening and a concurrent decrease of steady-state hTERT mRNA levels, attenuating their ability to form colonies in soft agar. Importantly, HMGA2 partially replaces the function of hTERT during the tumorigenic transformation of normal human fibroblasts. These findings are potentially clinically relevant, because HMGA2 expression is reported to be upregulated in a number of human cancers as telomere maintenance is essential for tumorigenesis.
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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.