ArticlePloS one2015
G9a Inhibition Induces Autophagic Cell Death via AMPK/mTOR Pathway in Bladder Transitional Cell Carcinoma.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Targeting histone modifiers in bladder cancer therapy - preclinical and clinical evidence.Nature reviews. Urology · 2024Review
- Molecular and functional anticancer effects of GLP/G9a inhibition by UNC0646 in MeWo melanoma cells.Heliyon · 2024Article
- Alternative splicing regulation and its therapeutic potential in bladder cancer.Frontiers in oncology · 2024Review
- The exploitation of host autophagy and ubiquitin machinery byAutophagy · 2023Review
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- Article
- Cinnamaldehyde induces autophagy-mediated cell death through ER stress and epigenetic modification in gastric cancer cells.Acta pharmacologica Sinica · 2022Article
- Role of Chromatin Modifying Complexes and Therapeutic Opportunities in Bladder Cancer.Bladder cancer (Amsterdam, Netherlands) · 2022Review
- Prediction of Prognosis and Recurrence of Bladder Cancer by ECM-Related Genes.Journal of immunology research · 2022Article
- Epigenetic regulation of autophagy: A key modification in cancer cells and cancer stem cells.World journal of stem cells · 2021Review
- BIX-01294, a G9a inhibitor, suppresses cell proliferation by inhibiting autophagic flux in nasopharyngeal carcinoma cells.Investigational new drugs · 2021Article
- G9a/GLP targeting in MM promotes autophagy-associated apoptosis and boosts proteasome inhibitor-mediated cell death.Blood advances · 2021Article
- Contrast effects of autophagy in the treatment of bladder cancer.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Insight into the multi-faceted role of the SUV family of H3K9 methyltransferases in carcinogenesis and cancer progression.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Epigenetic Regulation of Autophagy Beyond the Cytoplasm: A Review.Frontiers in cell and developmental biology · 2021Review
- SPAG6 silencing induces autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway.Oncology letters · 2020Article
- Novel G9a/DNMT first-in-class dual reversible inhibitor has potent antitumor effect in bladder cancer.Translational cancer research · 2020Article
- Targeting the Immune system and Epigenetic Landscape of Urological Tumors.International journal of molecular sciences · 2020Review
- EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation.International journal of biological sciences · 2020Article
- The combination of G9a histone methyltransferase inhibitors with erythropoietin protects heart against damage from acute myocardial infarction.American journal of translational research · 2020Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G9a has been reported to highly express in bladder transitional cell carcinoma (TCC) and G9a inhibition significantly attenuates cell proliferation, but the underlying mechanism is not fully understood. The present study aimed at examining the potential role of autophagy in the anti-proliferation effect of G9a inhibition on TCC T24 and UMUC-3 cell lines in vitro. We found that both pharmaceutical and genetical G9a inhibition significantly attenuated cell proliferation by MTT assay, Brdu incorporation assay and colony formation assay. G9a inhibition induced autophagy like morphology as determined by transmission electron microscope and LC-3 fluorescence assay. In addition, autophagy flux was induced by G9a inhibition in TCC cells, as determined by p62 turnover assay and LC-3 turnover assay. The autophagy induced positively contributed to the inhibition of cell proliferation because the growth attenuation capacity of G9a inhibition was reversed by autophagy inhibitors 3-MA. Mechanically, AMPK/mTOR pathway was identified to be involved in the regulation of G9a inhibition induced autophagy. Intensively activating mTOR by Rheb overexpression attenuated autophagy and autophagic cell death induced by G9a inhibition. In addition, pre-inhibiting AMPK by Compound C attenuated autophagy together with the anti-proliferation effect induced by G9a inhibition while pre-activating AMPK by AICAR enhanced them. In conclusion, our results indicate that G9a inhibition induces autophagy through activating AMPK/mTOR pathway and the autophagy induced positively contributes to the inhibition of cell proliferation in TCC cells. These findings shed some light on the functional role of G9a in cell metabolism and suggest that G9a might be a therapeutic target in bladder TCC in the future.
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