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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10761/3753

Data: 18-dic-2017
Autori: Barbagallo, Cristina
Titolo: LncRNA and circRNA expression profiles in tissues and serum exosomes of colorectal cancer patients and cell lines
Abstract: In the last few years several studies demonstrated the fundamental role of non-coding RNAs (ncRNAs) in tumor onset and progression. While the involvement and the mechanism of action of microRNAs (miRNAs) have been widely investigated, little is known about long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), which seem to act through a plethora of molecular mechanisms regulating essential biological processes, such as cell cycle, splicing, chromatin remodeling, apoptosis, adhesion and migration. LncRNAs are non-coding RNAs longer than 200 nucleotides, with or without 5 -cap and poly(A) tail; circRNAs are circular molecules lacking free ends and thus resistant to exonucleasic degradation, transcribed from protein-coding genes. Several evidences showed that aberrant expression of lncRNAs and circRNAs is associated with various tumors, including CRC. In our study we analysed through Real-Time PCR the expression of a set of 17 lncRNAs and 31 circRNAs selected from literature in 20 CRC tissues compared to normal adjacent tissues (NATs), and in serum exosomes of 20 CRC patients compared to 20 healthy individuals. We identified 8 ncRNAs (CCAT1, CCAT2, CDR1AS, HOTAIR, MALAT1, TUG1, UCA1 and ZEB2AS1) differentially expressed (DE) in tissues and 3 ncRNAs (circ16, TUG1 and UCA1) DE in serum exosomes. Through gene ontology analysis we verified the involvement of DE ncRNAs in pathways associated with tumor progression; we also evaluated the diagnostic accuracy of ncRNAs deregulated in serum exosomes through ROC curves, suggesting their possible application in CRC non-invasive diagnosis. We observed that inhibition of MAPK pathway, associated with CRC, altered the expression of HOTAIR, MALAT1, TUG1 and UCA1 in HCT-116 colon cancer cells treated with U0126 (MEK1/2 specific inhibitor) compared to untreated cells, suggesting a possible connection between ncRNAs and MAPKs. Also, we performed a computational analysis to identify mRNAs and miRNAs involved in CRC and characterized by correlation of expression and sequence complementarity with ncRNAs deregulated in CRC tissues. Finally, we performed in vitro functional assays by silencing UCA1 expression through ASOs in HCT-116 cells and analysed the expression of its mRNA and miRNA targets, aiming to investigate the eventual degradation triggered by the interaction between ncRNAs and their miRNA/mRNA targets. Our study provide new data about aberrant expression of ncRNAs in CRC and their involvement in carcinogenesis; further analyses will be necessary to fully understand ncRNA molecular mechanisms and to evaluate their possible application in CRC diagnosis and therapy.
InArea 06 - Scienze mediche

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