MicroRNA-195 acts as an anti-proliferative miRNA in human melanoma cells by targeting Prohibitin 1

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art_CIRILO_MicroRNA195_acts_as_an_antiproliferative_miRNA_in_human_2017.PDF (2.19 MB)
Citações na Scopus
23
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
BIOMED CENTRAL LTD
Autores
CORREA, Bruna Renata Silva
QIAO, Mei
PENALVA, Luiz Otavio Ferraz
Citação
BMC CANCER, v.17, article ID 750, 12p, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Melanoma is the most lethal type of skin cancer. Since chemoresistance is a significant barrier, identification of regulators affecting chemosensitivity is necessary in order to create new forms of intervention. Prohibitin 1 (PHB1) can act as anti-apoptotic or tumor suppressor molecule, depending on its subcellular localization. Our recent data shown that accumulation of PHB1 protects melanoma cells from chemotherapy-induced cell death. Lacking of post-transcriptional regulation of PHB1 could explain this accumulation. Interestingly, most of melanoma patients have down-regulation of microRNA-195. Here, we investigate the role of miR-195, its impact on PHB1 expression, and on chemosensitivity in melanoma cells. Methods: TCGA-RNAseq data obtained from 341 melanoma patient samples as well as a panel of melanoma cell lines were used in an expression correlation analysis between PHB1 and predicted miRNAs. miR-195 impact on PHB1 mRNA and protein levels and relevance of this regulation were investigated in UACC-62 and SK-MEL-5 melanoma lines by RT-qPCR and western blot, luciferase reporter and genetic rescue experiments. Cell proliferation, cell-cycle analysis and caspase 3/7 assay were performed to investigate the potential action of miR-195 as chemosensitizer in melanoma cells treated with cisplatin and temozolomide. Results: Analysis of the TCGA-RNAseq revealed a significant negative correlation (Pearson) between miR-195 and PHB1 expression. Moreover, RT-qPCR data showed that miR-195 is down-regulated while PHB1 is up-regulated in a collection of melanoma cells. We demonstrated that miR-195 regulates PHB1 directly by RT-qPCR and western blot in melanoma cells and luciferase assays. To establish PHB1 as a relevant target of miR-195, we conducted rescue experiments in which we showed that PHB1 transgenic expression could antagonize the suppressive effect miR-195 on the proliferation of melanoma cells. Finally, transfection experiments combined with drug treatments performed in the UACC-62 and SK-MEL-5 melanoma cells corroborated miR-195 as potential anti-proliferative agent, with potential impact in sensitization of melanoma cell death. Conclusions: This study support the role of miR-195 as anti-proliferative miRNA via targeting of PHB1 in melanoma cells.
Palavras-chave
Melanoma, microRNA-195, Prohibitin 1, Cisplatin, Temozolomide, Vemurafenib
URI
https://observatorio.fm.usp.br/handle/OPI/24240
Referências
  1. Akbani R, 2015, CELL, V161, P1681, DOI 10.1016/j.cell.2015.05.044
  2. Chapman PB, 2011, NEW ENGL J MED, V364, P2507, DOI 10.1056/NEJMoa1103782
  3. Deng HX, 2013, GENE, V518, P351, DOI 10.1016/j.gene.2012.12.103
  4. Doudican NA, 2017, ONCOGENE, V36, P423, DOI 10.1038/onc.2016.214
  5. Farazi TA, 2011, J PATHOL, V223, P102, DOI 10.1002/path.2806
  6. Fattore L, 2017, ONCOTARGET, V8, P22262, DOI 10.18632/oncotarget.14763
  7. Flavin RJ, 2009, MODERN PATHOL, V22, P197, DOI 10.1038/modpathol.2008.135
  8. Francisco G, 2013, MELANOMA RES, V23, P231, DOI 10.1097/CMR.0b013e3283612483
  9. Fraser Michael, 2003, Reprod Biol Endocrinol, V1, P66, DOI 10.1186/1477-7827-1-66
  10. Haas U, 2012, RNA BIOL, V9, P924, DOI 10.4161/rna.20497
  11. He JF, 2011, J BIOCHEM MOL TOXIC, V25, P404, DOI 10.1002/jbt.20396
  12. He XX, 2015, MOL BIOSYST, V11, P532, DOI 10.1039/c4mb00563e
  13. Ikediobi ON, 2006, MOL CANCER THER, V5, P2606, DOI 10.1158/1535-7163.MCT-06-0433
  14. Jakubowska A, 2012, BRIT J CANCER, V106, P2016, DOI 10.1038/bjc.2012.160
  15. Jiang L, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2015.40
  16. Jones DP, 2008, AM J PHYSIOL-CELL PH, V295, pC849, DOI 10.1152/ajpcell.00283.2008
  17. Kuersten S, 2013, WIRES RNA, V4, P617, DOI 10.1002/wrna.1173
  18. Lakomy R, 2011, CANCER SCI, V102, P2186, DOI 10.1111/j.1349-7006.2011.02092.x
  19. Leal MF, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0098583
  20. Li D, 2011, CLIN CANCER RES, V17, P1722, DOI 10.1158/1078-0432.CCR-10-1800
  21. Li N, 2017, CELL BIOL INT, V41, P622, DOI 10.1002/cbin.10765
  22. Lian B, 2013, CLIN CANCER RES, V19, P4488, DOI 10.1158/1078-0432.CCR-13-0739
  23. Lo JA, 2014, SCIENCE, V346, P945, DOI 10.1126/science.1253735
  24. Luan Z, 2014, MOL CANCER, V13, DOI 10.1186/1476-4598-13-38
  25. Mhaidat NM, 2007, BRIT J CANCER, V97, P1225, DOI 10.1038/sj.bjc.6604017
  26. Mirzaei H, 2016, EUR J CANCER, V53, P25, DOI 10.1016/j.ejca.2015.10.009
  27. Mishra S, 2010, FEBS J, V277, P3937, DOI 10.1111/j.1742-4658.2010.07809.x
  28. Patel N, 2010, P NATL ACAD SCI USA, V107, P2503, DOI 10.1073/pnas.0910649107
  29. Peng YT, 2015, APOPTOSIS, V20, P1135, DOI 10.1007/s10495-015-1143-z
  30. Qu J, 2015, J CELL PHYSIOL, V230, P535, DOI 10.1002/jcp.24366
  31. Rajalingam K, 2005, CELL CYCLE, V4, P1503
  32. Robert C, 2015, NEW ENGL J MED, V372, P320, DOI 10.1056/NEJMoa1412082
  33. Robinson MD, 2010, BIOINFORMATICS, V26, P139, DOI 10.1093/bioinformatics/btp616
  34. Siddik ZH, 2003, ONCOGENE, V22, P7265, DOI 10.1038/sj.onc.1206933
  35. Su DM, 2009, MOL CANCER THER, V8, P1292, DOI 10.1158/1535-7163.MCT-08-1030
  36. Sun XY, 2016, ONCOTARGET, V7, P53558, DOI 10.18632/oncotarget.10669
  37. Tentori L, 2013, TRENDS PHARMACOL SCI, V34, P656, DOI 10.1016/j.tips.2013.10.003
  38. Tortelli TC, 2017, ONCOTARGET, V8, P43114, DOI 10.18632/oncotarget.17810
  39. Ujifuku K, 2010, CANCER LETT, V296, P241, DOI 10.1016/j.canlet.2010.04.013
  40. Vennepureddy Adarsh, 2016, J Clin Med Res, V8, P63, DOI 10.14740/jocmr2424w
  41. Vo DT, 2012, MOL CANCER RES, V10, P143, DOI 10.1158/1541-7786.MCR-11-0208
  42. Vo DT, 2011, RNA BIOL, V8, P817, DOI 10.4161/rna.8.5.16041
  43. Wang S, 1999, ONCOGENE, V18, P3501, DOI 10.1038/sj.onc.1202684
  44. Yang G, 2013, ONCOL REP, V30, P877, DOI 10.3892/or.2013.2532
  45. Yang XY, 2012, ONCOL REP, V27, P250, DOI 10.3892/or.2011.1472

Coleções
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03