Non-coding RNA ZFAS1 Research Articles

Upregulation of long noncoding RNA ZFAS1 predicts poor prognosis and prompts invasion and metastasis in colorectal cancer

PurposeZFAS1 is a newly identified long non-coding RNA. The present study investigated the relationships of ZFAS1 expression with clinicalpathologic parameters and the prognosis of patients with colorectal cancer (CRC). The effects of ZFAS1 on cell migration, invasion and metastasis were also been evaluated in CRC cell lines. MethodsA total of 159 paired primary CRC tissues and adjacent noncancerous tissues (NCTs) were collected and were tested for the expression of ZFAS1. Cell migration and invasion were measured by wound-healing and Transwell assays, respectively. Tumor metastasis was assessed using a lung metastasis model of nude mouse. ResultsThe ZFAS1 expression was significantly upregulated in 47.8% (76 of 159) of cancerous tissues compared with NCTs(p<0.0001), and was higher in metastatic tumors than in corresponding primary CRC tumors (p=0.010). ZFAS1 expression in CRC was positively correlated with lymphatic invasion (p=0.045) and TNM stage (p=0.003). Patients with increased ZFAS1 expression showed shorter relapse-free survival and overall survival (p<0.05). Cox multivariate analyses confirmed that ZFAS1 expression is an independent prognostic factor in CRC (p<0.05). The knockdown of ZFAS1 decreased cell migration and invasive ability of LoVo and HCT116 cells in vitro (p<0.05). Moreover, silencing ZFAS1 expression inhibited the in vivo metastasis of CRC cells (p<0.05). ConclusionsThe expression of ZFAS1 is positively correlated with TNM stage and appears to be a new prognostic factor in CRC. ZFAS1 promptes cell migration, invasive and metastasis ability of CRC cells.

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

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.