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文献详情 >LncRNA UCA1, Upregulated in CR... 收藏

LncRNA UCA1, Upregulated in CRC Biopsies and Downregulated in Serum Exosomes, Controls mRNA Expression by RNA-RNA Interactions

作     者:Barbagallo, Cristina Brex, Duilia Caponnetto, Angela Cimigliaro, Matilde Scalia, Marina Magnano, Antonio Caltabiano, Rosario Barbagallo, Davide Biondi, Antonio Cappellani, Alessandro Basile, Francesco Di Pietro, Cinzia Purrello, Michele Ragusa, Marco 

作者机构:Univ Catania Sect Biol & Genet G Sichel Dept Biomed & Biotechnol Sci Via Santa Sofia 87 I-95123 Catania Italy Vittorio Emanuele Hosp Digest Endoscopy Serv I-95124 Catania Italy Univ Catania Dept Med & Surg Sci & Adv Technol GF Ingrassia I-95123 Catania Italy Univ Catania Vittorio Emanuele Hosp Dept Surg I-95124 Catania Italy IRCCS Assoc Oasi Maria SS Inst Res Mental Retardat & Brain Aging I-94018 Troina EN Italy 

出 版 物:《MOLECULAR THERAPY NUCLEIC ACIDS》 (Mol. Ther. Nucl. Acids)

年 卷 期:2018年第12卷

页      面:229-241页

核心收录:

基  金:University of Catania through Finanziamento della Ricerca 2014 2016/2018 Department Research Plan of University of Catania 

主  题:colorectal cancer ceRNA network circRNAs lncRNAs miRNAs LINC01764 TUG1 circHIPK3 CEBPB 

摘      要:Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) contribute to the onset of many neoplasias through RNA-RNA competitive interactions;in addition, they could be secreted by cancer cells into biological fluids, suggesting their potential diagnostic application. By analyzing the expression of 17 lncRNAs and 31 circRNAs in biopsies and serum exosomes from colorectal cancer (CRC) patients through qRT-PCR, we detected CCAT1, CCAT2, HOTAIR, and UCA1 upregulation and CDR1AS, MALAT1, and TUG1 downregulation in biopsies. In serum exosomes, UCA1 was downregulated, while circHIPK3 and TUG1 were upregulated. Combined receiver operating characteristic (ROC) curves of TUG1:UCA1 and circHIPK3:UCA1 showed high values of sensitivity and specificity. Through in vitro (i.e., RNA silencing and mitogen-activated protein kinase [MAPK] inhibition) and in silico analyses (i.e., expression correlation and RNA-RNA-binding prediction), we found that UCA1 could (1) be controlled by MAPKs through CEBPB;(2) sequester miR-135a, miR-143, miR-214, and miR-1271, protecting ANLN, BIRC5, IPO7, KIF2A, and KIF23 from microRNA (miRNA)-induced degradation;and (3) interact with mRNA 3 -UTRs, preventing miRNA binding. UCA1 and its co-regulated antisense LINC01764 could interact and reciprocally mask their own miRNA-binding sites. Functional enrichment analysis of the RNA-RNA network controlled by UCA1 suggested its potential involvement in cellular migration. The UCA1 regulatory axis would represent a promising target to develop innovative RNA-based therapeutics against CRC.

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