Discovery of Jaspamycin from marine-derived natural product based on MTA3 to inhibit hepatocellular carcinoma progression.
Carcinoma, Hepatocellular
/ drug therapy
Liver Neoplasms
/ drug therapy
Humans
Animals
Mice
Cell Proliferation
/ drug effects
Cell Movement
/ drug effects
Biological Products
/ pharmacology
Hep G2 Cells
Cell Line, Tumor
Antineoplastic Agents
/ pharmacology
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
/ drug effects
Disease Progression
Cell Survival
/ drug effects
Aquatic Organisms
/ chemistry
Neoplasm Proteins
Hepatocellular carcinoma
Jaspamycin
MTA3
Marine-derived anticancer agent
Pan-cancer
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 Oct 2024
25 Oct 2024
Historique:
received:
19
03
2024
accepted:
03
10
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Studies have underscored the pivotal role of metastasis-associated protein 3 (MTA3) as a cancer regulator, yet its potential as a drug target across cancers necessitates comprehensive evaluation. In this study, we analyzed MTA3 expression profiles to ascertain its diagnostic and prognostic value in pan-cancers, probing associations with genetic variations and immunological characteristics. Notably, liver hepatocellular carcinoma (LIHC) exhibited the most significant correlation with MTA3. By transfection of siRNA, interference of MTA3 affected HepG2 and Hepa1-6 cell viability and migration. Through drug screening and drug-likeness evaluation among marine-derived natural products, Jaspamycin was identified as a potential hepatocellular carcinoma treatment by targeting MTA3. By applying in vitro and in vivo experiment, the inhibitory effects of Jaspamycin on hepatocellular carcinoma viability, migration, and tumor progression were observed. To assess the potential of MTA3 as an anticancer drug target, MTA3 overexpression plasmid was transfected together with Jaspamycin treatment, and observed that MTA3 upregulation counteracted the inhibitory effects of Jaspamycin on hepatocarcinoma cell proliferation and migration, underscoring the efficacy of MTA3 as a drug target in hepatocellular carcinoma drug screening. This study highlights the clinical significance of MTA3 in pan-cancer, particularly in hepatocellular carcinoma. Additionally, it identifies Jaspamycin, a marine-derived compound with promising pharmacological properties, as an effective inhibitor of MTA3 activity, suggesting its potential for hepatocellular carcinoma treatment.
Identifiants
pubmed: 39455636
doi: 10.1038/s41598-024-75205-7
pii: 10.1038/s41598-024-75205-7
doi:
Substances chimiques
MTA3 protein, human
0
Biological Products
0
Antineoplastic Agents
0
Neoplasm Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25294Subventions
Organisme : National Natural Science Foundation of China
ID : 82104173
Organisme : Heilongjiang Province Ordinary University Youth Innovation Talent Cultivation
ID : UNPYSCT-2020159
Informations de copyright
© 2024. The Author(s).
Références
Ren, X. et al. Marine Natural products: a potential source of anti-hepatocellular carcinoma drugs. J. Med. Chem. 64(12), 7879–7899 (2021).
doi: 10.1021/acs.jmedchem.0c02026
pubmed: 34128674
Saini, N. et al. Marine-derived Natural products as Anticancer agents. Med. Chem. 19(6), 538–555 (2023).
doi: 10.2174/1573406419666221202144044
pubmed: 36476429
Khalifa, S. et al. Marine natural products: a source of novel anticancer drugs. Mar. Drugs 17(9), 491 (2019).
Lunt, N. The global challenge of cancer governance. World Med. Health Pol. 15(4), 672–681 (2023).
doi: 10.1002/wmh3.577
Weinstein, J. N. et al. The cancer genome atlas pan-cancer analysis project. Nat. Genet. 45(10), 1113–1120 (2013).
doi: 10.1038/ng.2764
pubmed: 24071849
pmcid: 3919969
Kumar, R. & Wang, R. A. Structure, expression and functions of MTA genes. Gene 582(2), 112–121 (2016).
doi: 10.1016/j.gene.2016.02.012
pubmed: 26869315
pmcid: 4785049
Ning, Z., Gan, J., Chen, C., Zhang, D. & Zhang, H. Molecular functions and significance of the MTA family in hormone-independent cancer. Cancer Metast Rev. 33(4), 901–919 (2014).
doi: 10.1007/s10555-014-9517-1
Du, L. et al. MTA3 represses cancer stemness by targeting the SOX2OT/SOX2 axis. Iscience 22, 353–368 (2019).
doi: 10.1016/j.isci.2019.11.009
pubmed: 31810000
pmcid: 6909183
Jiao, T. et al. MTA3 regulates malignant progression of colorectal cancer through wnt signaling pathway. Tumour Biol. 39(3), 1393394637 (2017).
doi: 10.1177/1010428317695027
Li, H. et al. Overexpression of MTA3 correlates with tumor progression in non-small cell lung cancer. PLoS ONE 8(6), e66679 (2013).
doi: 10.1371/journal.pone.0066679
pubmed: 23840517
pmcid: 3686714
Wu, L. et al. Genome-wide CRISPR screen identifies MTA3 as an inducer of gemcitabine resistance in pancreatic ductal adenocarcinoma. Cancer Lett. 548, 215864 (2022).
doi: 10.1016/j.canlet.2022.215864
pubmed: 35981571
Ge, T. et al. Crosstalk between metabolic reprogramming and epigenetics in cancer: updates on mechanisms and therapeutic opportunities. Cancer Commun. 42(11), 1049–1082 (2022).
doi: 10.1002/cac2.12374
Peng, S. et al. EGFR-TKI resistance promotes immune escape in lung cancer via increased PD-L1 expression. Mol. Cancer 18(1), 165 (2019).
doi: 10.1186/s12943-019-1073-4
pubmed: 31747941
pmcid: 6864970
Petrelli, F., Ghidini, M., Ghidini, A. & Tomasello, G. Outcomes following Immune checkpoint inhibitor treatment of patients with microsatellite instability-high cancers: a systematic review and Meta-analysis. Jama Oncol. 6(7), 1068–1071 (2020).
doi: 10.1001/jamaoncol.2020.1046
pubmed: 32407439
Bonneville, R. et al. Landscape of microsatellite instability across 39 cancer types. Jco. Precis. Oncol. 2017, PO.17.00073 (2017).
Malta, T. M. et al. Machine learning identifies stemness features associated with oncogenic dedifferentiation. Cell 173(2), 338–354 (2018).
doi: 10.1016/j.cell.2018.03.034
pubmed: 29625051
pmcid: 5902191
Vattem, C. & Pakala, S. B. Metastasis-associated protein 1: a potential driver and regulator of the hallmarks of cancer. J. Biosci. 47, 23 (2022).
Du, L., Ning, Z., Zhang, H. & Liu, F. Corepressor metastasis-associated protein 3 modulates epithelial-to-mesenchymal transition and metastasis. Chin. J. Cancer 36(1), 28 (2017).
doi: 10.1186/s40880-017-0193-8
pubmed: 28279208
pmcid: 5345190
Fujita, N. et al. MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell 113(2), 207–219 (2003).
doi: 10.1016/S0092-8674(03)00234-4
pubmed: 12705869
Fearon, E. R. Connecting estrogen receptor function, transcriptional repression, and E-cadherin expression in breast cancer. Cancer Cell 3(4), 307–310 (2003).
doi: 10.1016/S1535-6108(03)00087-4
pubmed: 12726856
Fujita, N. et al. MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation. Cell 119(1), 75–86 (2004).
doi: 10.1016/j.cell.2004.09.014
pubmed: 15454082
Yao, Z. et al. MTA3-SOX2 Module regulates cancer stemness and contributes to clinical outcomes of tongue carcinoma. Front. Oncol. 9, 816 (2019).
doi: 10.3389/fonc.2019.00816
pubmed: 31552166
pmcid: 6736560
Wang, B. et al. The HDAC2-MTA3 interaction induces nonsmall cell lung cancer cell migration and invasion by targeting c-Myc and cyclin D1. Mol. Carcinogen 62(11), 1630–1644 (2023).
doi: 10.1002/mc.23604
Chu, H. et al. MiR-495 regulates proliferation and migration in NSCLC by targeting MTA3. Tumour Biol. 35(4), 3487–3494 (2014).
doi: 10.1007/s13277-013-1460-1
pubmed: 24293376
Li, Q. et al. High glucose promotes hepatic fibrosis via miR–32/MTA3–mediated epithelial–to–mesenchymal transition. Mol. Med. Rep. 19(4), 3190–3200 (2019).
doi: 10.3892/mmr.2016.4904
pubmed: 30816482
pmcid: 6423609
Wang, C. et al. Overexpression of the metastasis-associated gene MTA3 correlates with tumor progression and poor prognosis in hepatocellular carcinoma. J. Gastroen Hepatol. 32(8), 1525–1529 (2017).
doi: 10.1111/jgh.13680
Zhao, L., Wang, Y. & Liu, Q. Catalpol inhibits cell proliferation, invasion and migration through regulating miR-22-3p/MTA3 signalling in hepatocellular carcinoma. Exp. Mol. Pathol. 109, 51–60 (2019).
doi: 10.1016/j.yexmp.2019.104265
pubmed: 31145886
Dyshlovoy, S. A. & Honecker, F. Marine compounds and cancer: updates 2022. Mar. Drugs 20(12), 759 (2022).
Jimenez, P. C. et al. Enriching cancer pharmacology with drugs of marine origin. Brit J. Pharmacol. 177(1), 3–27 (2020).
doi: 10.1111/bph.14876
Althagbi, H. I., Alarif, W. M., Al-Footy, K. O. & Abdel-Lateff, A. Marine-derived macrocyclic alkaloids (MDMAs): chemical and biological diversity. Mar. Drugs 18(7), 368 (2020).
Yang, S., Li, D., Liu, W. & Chen, X. Polysaccharides from marine biological resources and their anticancer activity on breast cancer. Rsc Med. Chem. 14(6), 1049–1059 (2023).
doi: 10.1039/D3MD00035D
pubmed: 37360387
pmcid: 10285744
Pereira, L. & Cotas, J. Therapeutic potential of polyphenols and other micronutrients of Marine Origin. Mar. Drugs 21(6), 323 (2023).
Elez, E. et al. First-in-human phase I study of the microtubule inhibitor plocabulin in patients with advanced solid tumors. Invest. New. Drug 37(4), 674–683 (2019).
doi: 10.1007/s10637-018-0674-x
Cui, J. et al. Synthesis and in vitro antiproliferative evaluation of some B-norcholesteryl Benzimidazole and Benzothiazole derivatives. Mar. Drugs 13(4), 2488–2504 (2015).
doi: 10.3390/md13042488
pubmed: 25913705
pmcid: 4413222
Li, J., Guo, C. & Wu, J. Fucoidan: biological activity in liver diseases. Am. J. Chin. Med. 48(7), 1617–1632 (2020).
doi: 10.1142/S0192415X20500809
pubmed: 33148007
Huang, K. et al. Traditional Chinese medicine (TCM) in the treatment of COVID-19 and other viral infections: efficacies and mechanisms. Pharmacol. Therapeut. 225, 107843 (2021).
doi: 10.1016/j.pharmthera.2021.107843
Bachmaier, S. et al. Nucleoside analogue activators of cyclic AMP-independent protein kinase a of Trypanosoma. Nat. Commun. 10(1), 1421 (2019).
doi: 10.1038/s41467-019-09338-z
pubmed: 30926779
pmcid: 6440977
Wang, D. et al. A Grand Challenge: unbiased phenotypic function of metabolites from Jaspis splendens against Parkinson’s disease. J. Nat. Prod. 79(2), 353–361 (2016).
doi: 10.1021/acs.jnatprod.5b00987
pubmed: 26883470
Zhang, Y. et al. Application of computational biology and artificial intelligence in drug design. Int. J. Mol. Sci. 23(21), 13568 (2022).