Abstract
Hepatoblastoma (HB) is the most common and aggressive malignant hepatic neoplasm in childhood and the therapeutic outcomes remain undesirable due to its recurrence and metastasis. Recently, long non-coding RNA (lncRNA) zinc finger antisense 1 (ZFAS1) has been reported to be an oncogenic gene in multiple cancers. However, the expression status and specific role of ZFAS1 involved in cancer progression of human HB remain unknown. This study aimed to identify the role of ZFAS1/miR-193a-3p/RALY axis in the development of HB. Here we showed that the expression of ZFAS1 was significantly upregulated in both HB tissues and cell lines. High ZFAS1 expression was significantly associated with aggressive tumor phenotypes and poorer overall survival in HB. In vitro and in vivo function assays indicated that silencing of ZFAS1 significantly suppressed HB cell proliferation and invasion. Furthermore, miR-193a-3p was identified to be the target of ZFAS1. Subsequently, RALY was confirmed to be regulated by miR-193a-3p/ZFAS1 axis. Mechanistically, our results indicated that the ZFAS1 participated to the progression of HB via regulating the HGF/c-Met signaling. Collectively, these data demonstrated that ZFAS1 acted as an oncogene to promote initiation and progression of HB by regulating miR-193a-3p/RALY (RALY Heterogeneous Nuclear Ribonucleoprotein) axis via HGF/c-Met Pathway, which provides an efficient marker and new therapeutic target for HB.
Highlights
Hepatoblastoma (HB) is one of the most common and highly invasive primary malignant liver tumor in pediatric patients, which accounts for approximately 50% of pediatric liver cancers, occurring mostly within the first 2 years of life (Kremer et al, 2014)
To draw a comprehensive conclusion, we further examined the expression of zinc finger antisense 1 (ZFAS1) in 70 pairs of matched HB and normal tissues by Quantitative RT-PCR (qRT-PCR) using the ZZU cohort
Long non-coding RNA-TUG1 correlated with tumor angiogenesis and progression in HB (Dong et al, 2016)
Summary
Hepatoblastoma (HB) is one of the most common and highly invasive primary malignant liver tumor in pediatric patients, which accounts for approximately 50% of pediatric liver cancers, occurring mostly within the first 2 years of life (Kremer et al, 2014). Recent studies have demonstrated that lncRNAs are aberrantly expressed in various human cancers (Guo et al, 2019; Li et al, 2019; Zhang and Fan, 2019), including HB (Dong et al, 2017). Accumulating evidences have shown that specific lncRNAs act as tumor suppressor genes or oncogenes via mediating tumor progression. Long non-coding RNA-CRNDE (Dong et al, 2017), TUG1 (Dong et al, 2016) and OIP5-AS1 (Zhang et al, 2018) promote oncogenesis in HB, while experimental verification shows that LINC01314 acts as a tumor suppressor in HB (Lv et al, 2018). There is not known reports about the clinical significance and underlying mechanism of ZFAS1 in the progression of HB
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