Alterations in microRNA (miRNA) expression have been reported in different cancers. We assessed the expression of 754 oncology-related miRNAs in esophageal adenocarcinoma (EAC) samples and evaluated their correlations with clinical parameters. We found that miR-221 and 483-3p were consistently upregulated in EAC patients vs. controls (Wilcoxon signed-rank test: miR-221 p < 0.0001; miR-483-3p p < 0.0001). Kaplan-Meier analysis showed worse cancer-related survival among all EAC patients expressing high miR-221 or miR-483-3p levels (log-rank p = 0.0025 and p = 0.0235, respectively). Higher miR-221 or miR-483-3p levels also correlated with advanced tumor stages (Mann-Whitney p = 0.0195 and p = 0.0085, respectively), and overexpression of miR-221 was associated with worse survival in low-risk EAC patients. Moreover, a significantly worse outcome was associated with the combined overexpression of miR-221 and miR-483-3p (log-rank p = 0.0410). To identify target genes affected by miRNA overexpression, we transfected the corresponding mimic RNA (miRVANA) for either miR-221 or miR-483-3p in a well-characterized esophageal adenocarcinoma cell line (OE19) and performed RNA-seq analysis. In the miRNA-overexpressing cells, we discovered a convergent dysregulation of genes linked to apoptosis, ATP synthesis, angiogenesis, and cancer progression, including a long non-coding RNA associated with oncogenesis, i.e., MALAT1. In conclusion, dysregulated miRNA expression, especially overexpression of miR-221 and 483-3p, was found in EAC samples. These alterations were connected with a lower cancer-specific patient survival, suggesting that these miRNAs could be useful for patient stratification and prognosis.
miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma / Bozzarelli, Isotta; Orsini, Arianna; Isidori, Federica; Mastracci, Luca; Malvi, Deborah; Lugaresi, Marialuisa; Fittipaldi, Silvia; Gozzellino, Livia; Astolfi, Annalisa; Räsänen, Jari; D’Errico, Antonia; Rosati, Riccardo; Fiocca, Roberto; Seri, Marco; Krishnadath, Kausilia K.; Bonora, Elena; Mattioli, Sandro. - In: CANCERS. - ISSN 2072-6694. - ELETTRONICO. - 16:3(2024), pp. 591.591-591.605. [10.3390/cancers16030591]
miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma
Orsini, Arianna;Isidori, Federica;Mastracci, Luca;Malvi, Deborah;Lugaresi, Marialuisa;Fittipaldi, Silvia;Gozzellino, Livia;Astolfi, Annalisa;D’Errico, Antonia;Fiocca, Roberto;Seri, Marco;Bonora, Elena
;Mattioli, Sandro
2024
Abstract
Alterations in microRNA (miRNA) expression have been reported in different cancers. We assessed the expression of 754 oncology-related miRNAs in esophageal adenocarcinoma (EAC) samples and evaluated their correlations with clinical parameters. We found that miR-221 and 483-3p were consistently upregulated in EAC patients vs. controls (Wilcoxon signed-rank test: miR-221 p < 0.0001; miR-483-3p p < 0.0001). Kaplan-Meier analysis showed worse cancer-related survival among all EAC patients expressing high miR-221 or miR-483-3p levels (log-rank p = 0.0025 and p = 0.0235, respectively). Higher miR-221 or miR-483-3p levels also correlated with advanced tumor stages (Mann-Whitney p = 0.0195 and p = 0.0085, respectively), and overexpression of miR-221 was associated with worse survival in low-risk EAC patients. Moreover, a significantly worse outcome was associated with the combined overexpression of miR-221 and miR-483-3p (log-rank p = 0.0410). To identify target genes affected by miRNA overexpression, we transfected the corresponding mimic RNA (miRVANA) for either miR-221 or miR-483-3p in a well-characterized esophageal adenocarcinoma cell line (OE19) and performed RNA-seq analysis. In the miRNA-overexpressing cells, we discovered a convergent dysregulation of genes linked to apoptosis, ATP synthesis, angiogenesis, and cancer progression, including a long non-coding RNA associated with oncogenesis, i.e., MALAT1. In conclusion, dysregulated miRNA expression, especially overexpression of miR-221 and 483-3p, was found in EAC samples. These alterations were connected with a lower cancer-specific patient survival, suggesting that these miRNAs could be useful for patient stratification and prognosis.File | Dimensione | Formato | |
---|---|---|---|
cancers-16-00591Bozzarelli.pdf
accesso aperto
Tipo:
Versione (PDF) editoriale
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione
3.15 MB
Formato
Adobe PDF
|
3.15 MB | Adobe PDF | Visualizza/Apri |
cancers-16-00591-s001.zip
accesso aperto
Tipo:
File Supplementare
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione
711.55 kB
Formato
Zip File
|
711.55 kB | Zip File | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.