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- Title
miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma.
- Authors
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
- Abstract
Simple Summary: Low survival rates and a growing incidence characterize esophageal adenocarcinoma (EAC). MicroRNAs (miRNAs) have been linked to the development and progression of cancer, according to earlier research. Our study showed a significant correlation between poor cancer–related survival, tumor recurrence, and advanced disease stages with the overexpression of miR–221 and miR–483–3p. In particular, we have found that in low–risk EAC patients, miR–221 overexpression was linked to a lower survival rate. Therefore, these findings may help define patient stratification and determine targeted treatment for EAC. 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.
- Subjects
STATISTICS; MICRORNA; MANN Whitney U Test; KAPLAN-Meier estimator; DESCRIPTIVE statistics; RESEARCH funding; DATA analysis; ESOPHAGEAL tumors
- Publication
Cancers, 2024, Vol 16, Issue 3, p591
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16030591