isomiRs, the sequence-variants of microRNA, are known to be tissue and cell type specific but their physiological role is largely unknown. In this study we explored for the first time the expression of isomiRs across different stage I epithelial ovarian cancer (EOC) histological subtypes, in order to shed new light on their biological role in tumor growth and progression. In a multi-centric retrospective cohort of tumor biopsies (n=215) we sequenced small RNAs finding 971 expressed miRNAs, 64% of which are isomiRs. Among them, 42 isomiRs showed a clear histotype specific pattern, confirming our previously identified miRNA markers (miR192/194 and miR30a-3p/5p for mucinous and clear cell subtypes respectively) and uncovering new biomarkers for all the five subtypes. Using integrative models, we found that the 38% of these miRNA expression alterations is the result of copy number variations while the 17% of differential transcriptional activities. Our work represents the first attempt to characterize isomiRs expression in stage I EOC within and across subtypes and to contextualize their alterations in the framework of the large genomic heterogeneity of this tumor.

Velle, A., Pesenti, C., Grassi, T., Beltrame, L., Martini, P., Jaconi, M., et al. (2022). A comprehensive investigation of histotype-specific microRNA and their variants in stage I epithelial ovarian cancers. INTERNATIONAL JOURNAL OF CANCER [10.1002/ijc.34408].

A comprehensive investigation of histotype-specific microRNA and their variants in stage I epithelial ovarian cancers

Fruscio, Robert;
2022

Abstract

isomiRs, the sequence-variants of microRNA, are known to be tissue and cell type specific but their physiological role is largely unknown. In this study we explored for the first time the expression of isomiRs across different stage I epithelial ovarian cancer (EOC) histological subtypes, in order to shed new light on their biological role in tumor growth and progression. In a multi-centric retrospective cohort of tumor biopsies (n=215) we sequenced small RNAs finding 971 expressed miRNAs, 64% of which are isomiRs. Among them, 42 isomiRs showed a clear histotype specific pattern, confirming our previously identified miRNA markers (miR192/194 and miR30a-3p/5p for mucinous and clear cell subtypes respectively) and uncovering new biomarkers for all the five subtypes. Using integrative models, we found that the 38% of these miRNA expression alterations is the result of copy number variations while the 17% of differential transcriptional activities. Our work represents the first attempt to characterize isomiRs expression in stage I EOC within and across subtypes and to contextualize their alterations in the framework of the large genomic heterogeneity of this tumor.
Articolo in rivista - Articolo scientifico
biomarker; histotype; miRNA; ovarian cancer; sequencing
English
Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future.
Velle, A., Pesenti, C., Grassi, T., Beltrame, L., Martini, P., Jaconi, M., et al. (2022). A comprehensive investigation of histotype-specific microRNA and their variants in stage I epithelial ovarian cancers. INTERNATIONAL JOURNAL OF CANCER [10.1002/ijc.34408].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/400001
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