CDK9 inhibition triggers MT2A-dependent apoptosis in HCC cells

Asghar U, Witkiewicz AK, Turner NC, Knudsen ES (2015) The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov 14:130–146. https://doi.org/10.1038/nrd4504

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bacon CW, D’Orso I (2019) CDK9: a signaling hub for transcriptional control. Transcription 10:57–75. https://doi.org/10.1080/21541264.2018.1523668

Article  CAS  PubMed  Google Scholar 

Blagosklonny MV (2023) Selective protection of normal cells from chemotherapy, while killing drug-resistant cancer cells. Oncotarget 14:193–206. https://doi.org/10.18632/oncotarget.28382

Article  PubMed  PubMed Central  Google Scholar 

Dass CR, Choong PF (2008) C-jun: pharmaceutical target for DNAzyme therapy of multiple pathologies. Pharmazie 63:411–414

CAS  PubMed  Google Scholar 

He XL, Hu YH, Chen JM, Zhang DQ, Yang HL, Zhang LZ, Mu YP, Zhang H, Chen GF, Liu W et al (2022) SNS-032 attenuates liver fibrosis by anti-active hepatic stellate cells via Inhibition of Cyclin dependent kinase 9. Front Pharmacol 13:1016552. https://doi.org/10.3389/fphar.2022.1016552

Article  CAS  PubMed  PubMed Central  Google Scholar 

Krizkova S, Fabrik I, Adam V, Hrabeta J, Eckschlager T, Kizek R (2009) Metallothionein–a promising tool for cancer diagnostics. Bratisl Lek Listy 110:93–97

CAS  PubMed  Google Scholar 

Krizkova S, Kepinska M, Emri G, Rodrigo MA, Tmejova K, Nerudova D, Kizek R, Adam V (2016) Microarray analysis of Metallothioneins in human diseases: a review. J Pharm Biomed Anal 117:464–473. https://doi.org/10.1016/j.jpba.2015.09.031

Article  CAS  PubMed  Google Scholar 

Krzeslak A, Forma E, Jozwiak P, Szymczyk A, Smolarz B, Romanowicz-Makowska H, Rozanski W, Brys M (2014) Metallothionein 2A genetic polymorphisms and risk of ductal breast cancer. Clin Exp Med 14:107–113. https://doi.org/10.1007/s10238-012-0215-4

Article  CAS  PubMed  Google Scholar 

Leitch AE, Lucas CD, Marwick JA, Duffin R, Haslett C, Rossi AG (2012) Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their Inhibition drives apoptosis to promote resolution of inflammation. Cell Death Differ 19:1950–1961. https://doi.org/10.1038/cdd.2012.80

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu H, Rice AP (2000) Genomic organization and characterization of promoter function of the human CDK9 gene. Gene 252:51–59. https://doi.org/10.1016/s0378-1119(00)00215-8

Article  CAS  PubMed  Google Scholar 

Liu H, Herrmann CH, Chiang K, Sung TL, Moon SH, Donehower LA, Rice AP (2010) 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair. Biochem Biophys Res Commun 397:245–250. https://doi.org/10.1016/j.bbrc.2010.05.092

Article  CAS  PubMed  PubMed Central  Google Scholar 

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390. https://doi.org/10.1056/NEJMoa0708857

Article  CAS  PubMed  Google Scholar 

Marshall NF, Price DH (1992) Control of formation of two distinct classes of RNA polymerase II elongation complexes. Mol Cell Biol 12:2078–2090. https://doi.org/10.1128/mcb.12.5.2078-2090.1992

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martin RD, Hebert TE, Tanny JC (2020) Therapeutic targeting of the general RNA polymerase II transcription machinery. Int J Mol Sci. https://doi.org/10.3390/ijms21093354

Article  PubMed  PubMed Central  Google Scholar 

Meloni G, Zovo K, Kazantseva J, Palumaa P, Vasak M (2006) Organization and assembly of metal-thiolate clusters in epithelium-specific metallothionein-4. J Biol Chem 281:14588–14595. https://doi.org/10.1074/jbc.M601724200

Article  CAS  PubMed  Google Scholar 

Nordberg M, Nordberg GF (2000) Toxicological aspects of Metallothionein. Cell Mol Biol (Noisy-le-grand) 46:451–463

CAS  PubMed  Google Scholar 

Richters A, Doyle SK, Freeman DB, Lee C, Leifer BS, Jagannathan S, Kabinger F, Koren JV, Struntz NB, Urgiles J et al (2021) Modulating androgen receptor-driven transcription in prostate cancer with selective CDK9 inhibitors. Cell Chem Biol 28:134–147e114. https://doi.org/10.1016/j.chembiol.2020.10.001

Article  CAS  PubMed  Google Scholar 

Rizzo A, Brunetti O, Brandi G (2024) Hepatocellular carcinoma immunotherapy: predictors of Response, Issues, and challenges. Int J Mol Sci. https://doi.org/10.3390/ijms252011091

Article  PubMed  PubMed Central  Google Scholar 

Saunders A, Core LJ, Lis JT (2006) Breaking barriers to transcription elongation. Nat Rev Mol Cell Biol 7:557–567. https://doi.org/10.1038/nrm1981

Article  CAS  PubMed  Google Scholar 

Shore SM, Byers SA, Maury W, Price DH (2003) Identification of a novel isoform of Cdk9. Gene 307:175–182. https://doi.org/10.1016/s0378-1119(03)00466-9

Article  CAS  PubMed  Google Scholar 

Starska K, Krzeslak A, Forma E, Olszewski J, Morawiec-Sztandera A, Aleksandrowicz P, Lewy-Trenda I, Brys M (2014) The – 5 A/G single-nucleotide polymorphism in the core promoter region of MT2A and its effect on allele-specific gene expression and Cd, Zn and Cu levels in laryngeal cancer. Toxicol Appl Pharmacol 280:256–263. https://doi.org/10.1016/j.taap.2014.08.016

Article  CAS  PubMed  Google Scholar 

Starska K, Brys M, Forma E, Olszewski J, Pietkiewicz P, Lewy-Trenda I, Danilewicz M, Krzeslak A (2015) The effect of Metallothionein 2A core promoter region single-nucleotide polymorphism on accumulation of toxic metals in sinonasal inverted papilloma tissues. Toxicol Appl Pharmacol 285:187–197. https://doi.org/10.1016/j.taap.2015.04.008

Article  CAS  PubMed  Google Scholar 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660

Article  CAS  PubMed  Google Scholar 

Tong Z, Mejia A, Veeranki O, Verma A, Correa AM, Dokey R, Patel V, Solis LM, Mino B, Kathkuda R et al (2019) Targeting CDK9 and MCL-1 by a new CDK9/p-TEFb inhibitor with and without 5-fluorouracil in esophageal adenocarcinoma. Ther Adv Med Oncol 11:1758835919864850. https://doi.org/10.1177/1758835919864850

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vasak M, Meloni G (2011) Chemistry and biology of mammalian Metallothioneins. J Biol Inorg Chem 16:1067–1078. https://doi.org/10.1007/s00775-011-0799-2

Article  CAS  PubMed  Google Scholar 

Vervoort SJ, Welsh SA, Devlin JR, Barbieri E, Knight DA, Offley S, Bjelosevic S, Costacurta M, Todorovski I, Kearney CJ et al (2021) The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer. Cell 184:3143–3162e3132. https://doi.org/10.1016/j.cell.2021.04.022

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wei D, Wang H, Zeng Q, Wang W, Hao B, Feng X, Wang P, Song N, Kan W, Huang G et al (2021) Discovery of potent and selective CDK9 degraders for targeting transcription regulation in triple-negative breast cancer. J Med Chem 64:14822–14847. https://doi.org/10.1021/acs.jmedchem.1c01350

Article  CAS  PubMed  Google Scholar 

Wu T, Qin Z, Tian Y, Wang J, Xu C, Li Z, Bian J (2020) Recent developments in the biology and medicinal chemistry of CDK9 inhibitors: an update. J Med Chem 63:13228–13257. https://doi.org/10.1021/acs.jmedchem.0c00744

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