Malignant cutaneous melanoma (CM) is a potentially lethal form of skin cancer whose worldwide incidence has been constantly increasing over the past decades. During their lifetime, about 8% of CM patients will develop multiple primary melanomas (MPMs), usually at a young age and within 3 years from the first tumor/diagnosis. With the aim of improving our knowledge on MPM biology and pathogenesis, we explored the miRNome of 24 single and multiple primary melanomas, including multiple tumors from the same patient, using a small RNA-sequencing approach. From a supervised analysis, 22 miRNAs were differentially expressed in MPM compared to single CM, including key miRNAs involved in epithelial–mesenchymal transition. The first and second melanoma from the same patient presented a different miRNA profile. Ten miRNAs, including miR-25-3p, 149-5p, 92b-3p, 211-5p, 125a-5p, 125b-5p, 205-5p, 200b-3p, 21-5p, and 146a-5p, were further validated in 47 single and multiple melanoma samples. Pathway enrichment analysis of miRNA target genes revealed a more differentiated and less invasive status of MPMs compared to CMs. Bioinformatic analyses at the miRNA isoform (isomiR) level detected a panel of highly expressed isomiRs belonging to miRNA families implicated in human tumorigenesis, including miR-200, miR-30, and miR-10 family. Moreover, we identified hsa-miR-125a-5p|0|−2 isoform as tenfold over-represented in melanoma than the canonical form and differentially expressed in MPMs arising in the same patient. Target prediction analysis revealed that the miRNA shortening could change the pattern of target gene regulation, specifically in genes implicated in cell adhesion and neuronal differentiation. Overall, we provided a putative and comprehensive characterization of the miRNA/isomiR regulatory network of MPMs, highlighting mechanisms of tumor development and molecular features differentiating this subtype from single melanomas.

Dika E., Broseghini E., Porcellini E., Lambertini M., Riefolo M., Durante G., et al. (2021). Unraveling the role of microRNA/isomiR network in multiple primary melanoma pathogenesis. CELL DEATH & DISEASE, 12(5), 473-473 [10.1038/s41419-021-03764-y].

Unraveling the role of microRNA/isomiR network in multiple primary melanoma pathogenesis

Dika E.
Primo
;
Broseghini E.;Porcellini E.;Lambertini M.;Riefolo M.;Durante G.;Roncarati R.;Misciali C.;Patrizi A.;Ferracin M.
Ultimo
2021

Abstract

Malignant cutaneous melanoma (CM) is a potentially lethal form of skin cancer whose worldwide incidence has been constantly increasing over the past decades. During their lifetime, about 8% of CM patients will develop multiple primary melanomas (MPMs), usually at a young age and within 3 years from the first tumor/diagnosis. With the aim of improving our knowledge on MPM biology and pathogenesis, we explored the miRNome of 24 single and multiple primary melanomas, including multiple tumors from the same patient, using a small RNA-sequencing approach. From a supervised analysis, 22 miRNAs were differentially expressed in MPM compared to single CM, including key miRNAs involved in epithelial–mesenchymal transition. The first and second melanoma from the same patient presented a different miRNA profile. Ten miRNAs, including miR-25-3p, 149-5p, 92b-3p, 211-5p, 125a-5p, 125b-5p, 205-5p, 200b-3p, 21-5p, and 146a-5p, were further validated in 47 single and multiple melanoma samples. Pathway enrichment analysis of miRNA target genes revealed a more differentiated and less invasive status of MPMs compared to CMs. Bioinformatic analyses at the miRNA isoform (isomiR) level detected a panel of highly expressed isomiRs belonging to miRNA families implicated in human tumorigenesis, including miR-200, miR-30, and miR-10 family. Moreover, we identified hsa-miR-125a-5p|0|−2 isoform as tenfold over-represented in melanoma than the canonical form and differentially expressed in MPMs arising in the same patient. Target prediction analysis revealed that the miRNA shortening could change the pattern of target gene regulation, specifically in genes implicated in cell adhesion and neuronal differentiation. Overall, we provided a putative and comprehensive characterization of the miRNA/isomiR regulatory network of MPMs, highlighting mechanisms of tumor development and molecular features differentiating this subtype from single melanomas.
2021
Dika E., Broseghini E., Porcellini E., Lambertini M., Riefolo M., Durante G., et al. (2021). Unraveling the role of microRNA/isomiR network in multiple primary melanoma pathogenesis. CELL DEATH & DISEASE, 12(5), 473-473 [10.1038/s41419-021-03764-y].
Dika E.; Broseghini E.; Porcellini E.; Lambertini M.; Riefolo M.; Durante G.; Loher P.; Roncarati R.; Bassi C.; Misciali C.; Negrini M.; Rigoutsos I.;...espandi
File in questo prodotto:
File Dimensione Formato  
2021_CDDIS-multiple-melanoma.pdf

accesso aperto

Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione 1.48 MB
Formato Adobe PDF
1.48 MB Adobe PDF Visualizza/Apri
41419_2021_3764_MOESM8_ESM.zip

accesso aperto

Tipo: File Supplementare
Licenza: Licenza per Accesso Aperto. Altra tipologia di licenza compatibile con Open Access
Dimensione 4.17 MB
Formato Zip File
4.17 MB Zip File Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/829308
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 16
social impact