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Small non-coding RNA deregulation in endometrial carcinogenesis

2015; Impact Journals LLC; Volume: 6; Issue: 7 Linguagem: Inglês

10.18632/oncotarget.2911

1949-2553

Maria Ravo, Angela Cordella, Antonio Rinaldi, Giuseppina Bruno, Elena Alexandrova, Pasquale Saggese, Giovanni Nassa, Giorgio Giurato, Roberta Tarallo, Giovanna Marchese, Francesca Rizzo, Claudia Stellato, Rossella Biancardi, Jacopo Troisi, Attilio Di Spiezio Sardo, Fulvio Zullo, Alessandro Weisz, Maurizio Guida,

MicroRNA in disease regulation

// Maria Ravo 1 , Angela Cordella 2 , Antonio Rinaldi 1 , Giuseppina Bruno 1 , Elena Alexandrova 1, 3 , Pasquale Saggese 1 , Giovanni Nassa 1 , Giorgio Giurato 1 , Roberta Tarallo 1 , Giovanna Marchese 1, 3 , Francesca Rizzo 1 , Claudia Stellato 1 , Rossella Biancardi 4 , Jacopo Troisi 4 , Attilio Di Spiezio Sardo 5 , Fulvio Zullo 5 , Alessandro Weisz 1, 6 , Maurizio Guida 4 1 Laboratory of Molecular Medicine and Genomics, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy 2 Fondazione IRCCS SDN, Napoli, Italy 3 Genomix4Life Srl, Spin-Off of the Laboratory of Molecular Medicine and Genomics, University of Salerno, Baronissi, Italy 4 Department of Medicine and Surgery and Division of Gynecology and Obstetrics, "SS. Giovanni di Dio e Ruggi d'Aragona - Schola Medica Salernitana", University of Salerno Hospital, Salerno, Italy 5 Department of Gynecology and Obstetrics and Pathophysiology of Human Reproduction, University of Naples "Federico II", Napoli, Italy 6 Division of Molecular Pathology and Medical Genomics, "SS. Giovanni di Dio e Ruggi d'Aragona - Schola Medica Salernitana", University of Salerno Hospital, Salerno, Italy Correspondence to: Maurizio Guida, e-mail: maguida@unisa.it Alessandro Weisz, e-mail: aweisz@unisa.it Keywords: small non-coding RNA, endometrial cancer, miRNAs, piRNAs, snoRNAs Received: November 02, 2014 Accepted: December 11, 2014 Published: February 28, 2015 ABSTRACT Small non-coding RNAs (sncRNAs) represent a heterogeneous group of <200nt-long transcripts comprising microRNAs, PIWI-interacting RNAs (piRNAs) and small-nucleolar-RNAs (snoRNAs) involved in physiological and pathological processes such as carcinogenesis and tumor progression. Aberrant sncRNA expression in cancer has been associated with specific clinical phenotypes, grading, staging, metastases development and resistance to therapy. Aim of the present work is to study the role of sncRNAs in endometrial carcinogenesis. Changes in sncRNA expression were identified by high-throughput genomic analysis of paired normal, hyperplastic and cancerous endometrial tissues obtained by endometrial biopsies ( n = 10). Using smallRNA sequencing and microarrays we identified significant differences in sncRNA expression pattern between normal, hyperplastic and neoplastic endometrium. This led to the definition of a sncRNA signature (129 microRNAs, 2 of which not previously described, 10 piRNAs and 3 snoRNAs) of neoplastic transformation. Functional bioinformatics analysis identified as downstream targets multiple signaling pathways potentially involved in the hyperplastic and neoplastic tissue responses, including Wnt/β-catenin, and ERK/MAPK and TGF-β-Signaling. Considering the regulatory role of sncRNAs, this newly identified sncRNA signature is likely to reflect the events leading to endometrial cancer, which can be exploited to dissect the carcinogenic process including novel biomarkers for early and non-invasive diagnosis of these tumors.