Biological function of UCA1 in hepatocellular carcinoma and its clinical significance: Investigation with in vitro and meta-analysis

Urothelial cancer associated 1 (UCA1) was upregulated in hepatocellular carcinoma (HCC) tissues and cell lines, and the expression of UCA1 was associated with several clinical features and malignant behaviours in HCC. However, none of these findings completely interpreted the role of UCA1 in HCC. We conducted this investigation to validate the expression of UCA1 and its relationship with Tumor Node Metastasis (TNM) stage in 41 HCC tissues and their paired noncancerous adjacent tissues by real-time qPCR. Furthermore, we also explored the biological functions of UCA1 in vitro with HCC cell lines. Most importantly, we conducted a comprehensive meta-analysis and bioinformatics investigation based on peer-reviewed literature and in silico approaches to further summarise the clinical value and functions of UCA1 in HCC. UCA1 expression was remarkably upregulated in HCC tissues, and its expression was profoundly higher in advanced stages than in early stages. Reducing the expression levels of UCA1 suppressed the proliferation and induced apoptosis of HCC cells. Furthermore, the present meta-analysis validated that up-regulated UCA1 was closely related to larger tumour size and advanced TNM stages, and the overexpression of UCA1 was significantly correlated with a shorter OS. Additionally, according to GO analysis, the target genes were found concentrated in the following biological processes: extracellular matrix organisation, cilium assembly and cilium morphogenesis. KEGG pathway analysis showed that the UCA1-related genes were significantly enriched in the following pathways: hippo signalling pathway, bile secretion and gastric acid secretion. This evidence hinted that UCA1 could play an indispensable proliferation-related key role in HCC via the hippo signalling pathway. However, the exact molecular mechanism needs to be verified with future functional experiments.