LncRNAs and 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, UCA1 upregulation and CDR1AS, MALAT1, TUG1 downregulation in biopsies. In serum exosomes, UCA1 was downregulated, while circHIPK3 and TUG1 were upregulated. Combined ROC curves of TUG1:UCA1 and circHIPK3:UCA1 showed high values of sensitivity and specificity. Through in vitro (i.e., RNA silencing, MAPK inhibition) and in silico analyses (i.e., expression correlation, RNA-RNA binding prediction), we found that UCA1 could (1) be controlled by MAPKs through CEBPB, (2) sequester miR-135a, miR-143, miR-214, miR-1271, protecting ANLN, BIRC5, IPO7, KIF2A, KIF23 from miRNA-induced degradation; (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. UCA1 regulatory axis would represent a promising target to develop innovative RNA-based therapeutics against CRC. References 1) Barbagallo C et al. LncRNA UCA1, upregulated in CRC biopsies and downregulated in serum exosomes, controls mRNA expression by RNA-RNA interactions. Molecular Therapy - Nucleic Acid, 2018 Volume 12, 7 September 2018, Pages 229–241. https://doi.org/10.1016/j.omtn.2018.05.009. 2) Ragusa M, et al. Molecular Crosstalking among Noncoding RNAs: A New Network Layer of Genome Regulation in Cancer. Int J Genomics. 2017;2017:4723193. 3) Ragusa M et al. Non-coding landscapes of colorectal cancer. World J Gastroenterol. 2015;21(41):11709-39.
LncRNA UCA1, upregulated in CRC biopsies and downregulated in serum exosomes, controls mRNA expression by RNA-RNA interactions
Barbagallo C;Brex D;Caponnetto A;Cirnigliaro M;Scalia M;Caltabiano R;Barbagallo D;Biondi A;Cappellani A;Basile F;Di Pietro C;Purrello M;Ragusa M
2018-01-01
Abstract
LncRNAs and 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, UCA1 upregulation and CDR1AS, MALAT1, TUG1 downregulation in biopsies. In serum exosomes, UCA1 was downregulated, while circHIPK3 and TUG1 were upregulated. Combined ROC curves of TUG1:UCA1 and circHIPK3:UCA1 showed high values of sensitivity and specificity. Through in vitro (i.e., RNA silencing, MAPK inhibition) and in silico analyses (i.e., expression correlation, RNA-RNA binding prediction), we found that UCA1 could (1) be controlled by MAPKs through CEBPB, (2) sequester miR-135a, miR-143, miR-214, miR-1271, protecting ANLN, BIRC5, IPO7, KIF2A, KIF23 from miRNA-induced degradation; (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. UCA1 regulatory axis would represent a promising target to develop innovative RNA-based therapeutics against CRC. References 1) Barbagallo C et al. LncRNA UCA1, upregulated in CRC biopsies and downregulated in serum exosomes, controls mRNA expression by RNA-RNA interactions. Molecular Therapy - Nucleic Acid, 2018 Volume 12, 7 September 2018, Pages 229–241. https://doi.org/10.1016/j.omtn.2018.05.009. 2) Ragusa M, et al. Molecular Crosstalking among Noncoding RNAs: A New Network Layer of Genome Regulation in Cancer. Int J Genomics. 2017;2017:4723193. 3) Ragusa M et al. Non-coding landscapes of colorectal cancer. World J Gastroenterol. 2015;21(41):11709-39.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
