Musashi-1 regulates cell cycle and confers resistance to cisplatin treatment in Group 3/4 medulloblastomas cells

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Tipo de produção
article
Data de publicação
2023
Título da Revista
ISSN da Revista
Título do Volume
Editora
SPRINGER JAPAN KK
Autores
CHAGAS, Pablo Shimaoka
VERONEZ, Luciana Chain
SOUSA, Graziella Ribeiro de
CRUZEIRO, Gustavo Alencastro Veiga
CORREA, Carolina Alves Pereira
SAGGIORO, Fabiano Pinto
QUEIROZ, Rosane Gomes de Paula
BRANDALISE, Silvia Regina
CARDINALLI, Izilda Aparecida
Citação
HUMAN CELL, v.36, n.6, p.2129-2139, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Groups (Grp) 3 and 4 are aggressive molecular subgroups of medulloblastoma (MB), with high rates of leptomeningeal dissemination. To date, there is still a paucity of biomarkers for these subtypes of MBs. In this study, we investigated the clinical significance and biological functions of Musashi-1 (MSI1) in Grp3 and Grp4-MBs. First, we assessed the expression profile of MSI1 in 59 primary MB samples (15-WNT, 18-SHH, 9-Grp3, and 17-Grp4 subgroups) by qRT-PCR. MSI1 mRNA expression levels were also validated in an additional public dataset of MBs (GSE85217). The ROC curve was used to validate the diagnostic standards of MSI1 expression. Next, the potential correlated cell-cycle genes were measured by RNA-Seq. Cell cycle, cell viability, and apoptosis were evaluated in a Grp3/Grp4 MB cell line after knockdown of MSI1 and cisplatin treatment. We identified an overexpression of MSI1 with a high accuracy to discriminate Grp3/Grp4-MBs from non-Grp3/Grp4-MBs. We identified that MSI1 knockdown not only triggered transcriptional changes in the cell-cycle pathway, but also affected G2/M phase in vitro, supporting the role of knockdown of MSI1 in cell-cycle arrest. Finally, MSI1 knockdown decreased cell viability and sensitized D283-Med cells to cisplatin treatment by enhancing cell apoptosis. Based on these findings, we suggest that MSI1 modulates cell-cycle progression and may play a role as biomarker for Grp3/Grp4-MBs. In addition, MSI1 knockdown combined with cisplatin may offer a potential strategy to be further explored in Grp3/Grp4-MBs.
Palavras-chave
Medulloblastoma, Grp3-MB, Grp4-MBs, RNA-binding protein, Musashi-1
Referências
  1. Baroni M, 2021, CANCERS, V13, DOI 10.3390/cancers13071494
  2. Bley N, 2021, BIOLOGY-BASEL, V10, DOI 10.3390/biology10050407
  3. Cavalli FMG, 2017, CANCER CELL, V31, P737, DOI 10.1016/j.ccell.2017.05.005
  4. Chiou GY, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-02057-9
  5. Cragle CE, 2019, J BIOL CHEM, V294, P10969, DOI 10.1074/jbc.RA119.007220
  6. Dahlrot RH, 2013, J NEURO-ONCOL, V115, P453, DOI 10.1007/s11060-013-1246-8
  7. das Chagas PF, 2022, J MOL NEUROSCI, V72, P633, DOI 10.1007/s12031-021-01942-3
  8. das Chagas PF, 2020, J GENE MED, V22, DOI 10.1002/jgm.3136
  9. FRIEDMAN HS, 1985, J NEUROPATH EXP NEUR, V44, P592, DOI 10.1097/00005072-198511000-00005
  10. Funakoshi Y, 2023, CANCER SCI, V114, P741, DOI 10.1111/cas.15691
  11. Götte M, 2011, INT J CANCER, V129, P2042, DOI 10.1002/ijc.25856
  12. da Silva PBG, 2016, CYTOTECHNOLOGY, V68, P1545, DOI 10.1007/s10616-015-9914-5
  13. Gu ZG, 2016, BIOINFORMATICS, V32, P2847, DOI 10.1093/bioinformatics/btw313
  14. Hovestadt V, 2019, NATURE, V572, P74, DOI 10.1038/s41586-019-1434-6
  15. Kabir TF, 2020, IMMUNOTARGETS THER, V9, P57, DOI 10.2147/ITT.S198162
  16. Kaneko Y, 2000, DEV NEUROSCI-BASEL, V22, P139, DOI 10.1159/000017435
  17. Kim D, 2019, NAT BIOTECHNOL, V37, P907, DOI 10.1038/s41587-019-0201-4
  18. Kudinov AE, 2017, CLIN CANCER RES, V23, P2143, DOI 10.1158/1078-0432.CCR-16-2728
  19. Li Jie, 2019, Nan Fang Yi Ke Da Xue Xue Bao, V39, P1436, DOI 10.12122/j.issn.1673-4254.2019.12.07
  20. Lin JC, 2019, NEOPLASIA, V21, P459, DOI 10.1016/j.neo.2019.02.006
  21. LOVE MI, 2014, GENOME BIOL, V15, DOI 10.1186/S13059-014-0550-8
  22. MacNicol MC, 2011, CELL CYCLE, V10, P39, DOI 10.4161/cc.10.1.14388
  23. Martins-da-Silva A, 2022, CELL MOL NEUROBIOL, DOI 10.1007/s10571-022-01217-4
  24. Matthews HK, 2022, NAT REV MOL CELL BIO, V23, P74, DOI 10.1038/s41580-021-00404-3
  25. Niu JB, 2017, ONCOL LETT, V14, P5271, DOI 10.3892/ol.2017.6870
  26. Northcott PA, 2019, NAT REV DIS PRIMERS, V5, DOI 10.1038/s41572-019-0063-6
  27. Ohyama T, 2012, NUCLEIC ACIDS RES, V40, P3218, DOI 10.1093/nar/gkr1139
  28. Okano H, 2002, J CELL SCI, V115, P1355
  29. Okano H, 2005, EXP CELL RES, V306, P349, DOI 10.1016/j.yexcr.2005.02.021
  30. PACKER RJ, 1994, J NEUROSURG, V81, P690, DOI 10.3171/jns.1994.81.5.0690
  31. Ramaswamy V, 2016, ACTA NEUROPATHOL, V131, P821, DOI 10.1007/s00401-016-1569-6
  32. Sakakibara S, 2001, J NEUROSCI, V21, P8091, DOI 10.1523/JNEUROSCI.21-20-08091.2001
  33. Sakakibara S, 1997, J NEUROSCI, V17, P8300
  34. Schmittgen TD, 2008, NAT PROTOC, V3, P1101, DOI 10.1038/nprot.2008.73
  35. Sharma T, 2019, ACTA NEUROPATHOL, V138, P309, DOI 10.1007/s00401-019-02020-0
  36. Shou ZX, 2017, ONCOL LETT, V13, P3556, DOI 10.3892/ol.2017.5879
  37. Toda M, 2001, GLIA, V34, P1, DOI 10.1002/glia.1034
  38. Cruzeiro GAV, 2019, ACTA NEUROPATHOL COM, V7, DOI 10.1186/s40478-019-0681-y
  39. Vo DT, 2012, AM J PATHOL, V181, P1762, DOI 10.1016/j.ajpath.2012.07.031