ZFPL1 drives hepatocellular carcinoma through CLDN3 in WNT signaling pathway
Massive studies have been applied in exploring the factors driving pathogenesis, progression and metastasis of hepatocellular carcinoma. However these studies were inefficient in disclosing the fundamental mechanism which promotes hepatocellular carcinoma. Zinc and zinc-finger proteins have been important in extensive biological processes for human. Supervised machine learning using bootstrapping algorithm on GEO and TCGA transcriptome data for hepatocellular carcinoma identified zinc-finger like protein ZFPL1 as potential hepatocellular carcinoma driver. Further studies validated ZFPL1 significantly promoted progression and metastasis of hepatocellular carcinoma. We performed RNA-seq on si-ZFPL1 xenograft tissue and identified CLDN3 as potential target gene for ZFPL1. Further experiments confirmed interaction between ZFPL1 and WNT signaling pathway markers. Conclusively, these studies indicated the effect and mechanism of ZFPL1 on promoting progression and metastasis of hepatocellular carcinoma and might gap the bridge between zinc-finger like proteins and hepatocellular carcinoma. Overall design: We used Trizol Reagent (Invitrogen Life Technologies) to extract total RNA in control group (n=3) and siZFPL1 group (n=3). The sequencing library was prepared using the TruSeq RNA sample preparation kit (Illumina, USA) and sequenced at the Hiseq platform (Illumina) of Shanghai Personal Biotechnology Co. LTD. (Shanghai, China). After screening for CutAdapt-based 3'end adapter sequences or reads with average quality score lower than Q20, the high-quality sequences were compared with the reference genome (Assembly GRCm38). The processed data were then normalized and derepeated. Finally fold change and p-value for Students' t-test were calculated for control and siZFPL1 groups.