Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer

Abstract

We determined expression of 83 long non-coding RNAs (lncRNAs) and identified ZFAS1 to be significantly up-regulated in colorectal cancer (CRC) tissue. In cohort of 119 CRC patients we observed that 111 cases displayed at least two-times higher expression of ZFAS1 in CRC compared to paired normal colorectal tissue (P < 0.0001). By use of CRC cell lines (HCT116+/+, HCT116−/− and DLD-1) we showed, that ZFAS1 silencing decreases proliferation through G1-arrest of cell cycle, and also tumorigenicity of CRC cells. We identified Cyclin-dependent kinase 1 (CDK1) as interacting partner of ZFAS1 by pull-down experiment and RNA immunoprecipitation. Further, we have predicted by bioinformatics approach ZFAS1 to sponge miR-590-3p, which was proved to target CDK1. Levels of CDK1 were not affected by ZFAS1 silencing, but cyclin B1 was decreased in both cell lines. We observed significant increase in p53 levels and PARP cleavage in CRC cell lines after ZFAS1 silencing indicating increase in apoptosis. Our data suggest that ZFAS1 may function as oncogene in CRC by two main actions: (i) via destabilization of p53 and through (ii) interaction with CDK1/cyclin B1 complex leading to cell cycle progression and inhibition of apoptosis. However, molecular mechanisms behind these interactions have to be further clarified.

Signature consist of nine differentially methylated gene pairs to predict the prognosis for stage II colorectal cancer patients

“…Expression level of NDRG4 also has been found strongly associated with the prediction and prognosis of colorectal cancer. Evidence suggested E2F1, BMP3 and ABL1 are associated with the progression of CRC, but mostly induced by non-coding RNAs [22][23][24]. These findings further supported the reliability of the prognosis ability of our conducted 9-gene-pair signature.…”

Transcriptome and long noncoding RNA sequencing of three extracellular vesicle subtypes released from the human colon cancer LIM1863 cell line

“…Antisense lncRNA AC007193.8 uniquely distributed to sMVs, RUSC1-AS1, TM4SF1-AS1, DLGAP1-AS1 and DLGAP1-AS1to A33-Exos, while SETD5-AS1, DNAJC27-AS1 and TTC28-AS1 selectively distributed to EpCAM-Exos. Of these antisense lncRNA ZFAS1, which has been reported in breast cancer tissue55, liver cancer56 and CRC57, is thought to function as an oncogene by destabilisation of p53 and interaction through the CDK1/cyclin B1 complex leading to cell cycle progression and inhibition of apoptosis57.…”

Upregulation of long noncoding RNA zinc finger antisense 1 enhances epithelial–mesenchymal transition in vitro and predicts poor prognosis in glioma

“…28 However, recent studies have shown that ZFAS1 was amplified in hepatocellular carcinoma, colorectal and gastric cancer, and associated with their poor prognosis. 25,29,30 However, the implication of ZFAS1 in glioma progression was still unclear. In this study, we investigated the expression of lncRNA ZFAS1 in glioma tissues as well as in normal brain tissues and further explored the relationship between ZFAS1 and clinicopathological features as well as prognosis of glioma patients.…”