Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

miRNA-221 and miRNA-483-3p Dysregulation Correlated with Poor Survival in Esophageal Adenocarcinoma

Isotta Bozzarelli
,
Federica Isidori
,
Arianna Orsini
,
Luca Mastracci
,
Deborah Malvi
ORCID logo ,
Marialuisa Lugaresi
ORCID logo ,
Silvia Fittipaldi
,
Henna Soderstrom
,
Jari Räsänen
ORCID logo ,
Antonietta D'Errico
ORCID logo ,
Anna Tomezzoli
,
Riccardo Rosati
ORCID logo ,
Roberto Fiocca
ORCID logo ,
Marco Seri
ORCID logo ,
Kausilia Krishnawatie Krishnadath
,
Elena Bonora
* ,
Sandro Mattioli
Version 1 : Received: 11 December 2023 / Approved: 11 December 2023 / Online: 11 December 2023 (16:18:59 CET)

A peer-reviewed article of this Preprint also exists.

Bozzarelli, I.; Orsini, A.; Isidori, F.; Mastracci, L.; Malvi, D.; Lugaresi, M.; Fittipaldi, S.; Gozzellino, L.; Astolfi, A.; Räsänen, J.; D’Errico, A.; Rosati, R.; Fiocca, R.; Seri, M.; Krishnadath, K.K.; Bonora, E.; Mattioli, S. miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma. Cancers 2024, 16, 591. Bozzarelli, I.; Orsini, A.; Isidori, F.; Mastracci, L.; Malvi, D.; Lugaresi, M.; Fittipaldi, S.; Gozzellino, L.; Astolfi, A.; Räsänen, J.; D’Errico, A.; Rosati, R.; Fiocca, R.; Seri, M.; Krishnadath, K.K.; Bonora, E.; Mattioli, S. miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma. Cancers 2024, 16, 591.

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) and evaluated their correlations with clinical parameters. We found that miR-221 and 483-3p were consistently upregulated in EAC cases 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 in patients expressing high miR-221 or miR-483-3p levels in all EACs (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). Moreover, we found that overexpression of miR-221 was associated with worse survival in the low-risk EAC group. 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 modified by miRNAs, we evaluatedtheir expression in different EAC cell lines, we transfected the corresponding mimic RNA (miRVANA) for either miR-221 or miR-483-3p and performed RNA-seq analysis. We found converging dysregulated genes involved in cancer progression, apoptosis, ATP synthesis and angiogenesis in miRNA-overexpressing cell lines, including a long non-coding RNA associated with oncogenesis, i.e., MALAT1. In conclusion, miR-221 and 483-3p overexpression in EAC correlated with low cancer-related survival, indicating that they might be considered new biomarkers for patient stratification.

Keywords

Esophageal adenocarcinoma; microRNA; miR-221; miR-483-3p

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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