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

Abstract

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.

Long Non-Coding RNA Urothelial Carcinoma Associated 1 Promotes Proliferation, Migration and Invasion of Osteosarcoma Cells by Regulating microRNA-182

“…3A, sh-UCA1 transfection notably up-regulated the expression levels of miR-182, miR-183, miR-133b, miR-199a-3p, miR-124, miR-646 and miR-100 in OS-732 cells (P < 0.05 or P < 0.01), but had no significant effects on miR-124 and miR-135b expression levels. Previous studies demonstrated that miR-144, miR-18a and miR-1271 were associated with UCA1 [23][24][25]. So, we also detected the expression levels of miR-144, miR-18a and miR-1271 in OS-732 cells after UCA1 knockdown.…”

“…Zhu et al proved that UCA1 desensitized breast cancer cells to trastuzumab through impeding miR-18a expression [24]. Barbagallo et al indicated that UCA1 was up-regulated in colon rectal cancer and controlled the expression of miR-1271 [25]. In the present study, we found that knockdown of UCA1 significantly increased the expression of miR-182 miR-183, miR-133b, miR-199a-3p, miR-124, miR-646, miR-100, miR-144 and miR-18a in OS-732 cells, but had no significant effects on miR-124, miR-135b and miR-1271 expression levels.…”

Identification of functional lncRNAs in gastric cancer by integrative analysis of GEO and TCGA data

“…The expression of lncRNA UCA1 has been reported to be upregulated in many cancers, including breast cancer, colorectal cancer, hepatocellular carcinoma and GC . Interestingly, lncRNA UCA1 was found to be participating in cell cycle by targeting mRNA CCNE1 and CDK1 through miR‐107 as well.…”

Sp1 Induced Long Non-coding Rna Agap2-as1 Promotes Cholangiocarcinoma Proliferation via Silencing of Cdkn1a

“…Although many of its abnormalities are known to be expressed in human cancer, the related molecular mechanisms are not fully understood. It is reported that lncRNA can affect the biological function of cancer cells by regulating the expression of target genes [27]. In this experiment, In addition, we found that the transcription factor SP1 can induce AGAP2-AS1,then we studied the expression of related target genes after knockdown of AGAP2-AS1 in CCA cells, and found that the expression of tumor suppressor gene CDKN1A was significantly increased after knockdown of AGAP2-AS1.…”