Abstract
Hepatocellular carcinoma (HCC) is the fifth common cause of tumor-related death worldwide. ZFP36, a RNA-binding protein, decreases in many cancers and its role in HCC remains unclear. This study aimed to investigate the underlying mechanisms by which ZFP36 inhibited HCC progression and increased fluorouracil (5-Fu) sensitivity. We found that ZFP36 was downregulated and PRC1 was upregulated in HCC tissues compared with adjacent non-tumor tissues. In vitro investigation presented that ZFP36 acted as a tumor suppressor, while overexpression of PRC1 increased cell proliferation, colony formation and invasion. Further investigations demonstrated that overexpression of ZFP36 inhibited tumor growth and promoted 5-Fu sensitivity in xenograft tumor mice model, which could be reversed when PRC1 overexpressed simultaneously. Luciferase reporter assays and Ribonucleoprotein immunoprecipitation analysis indicated that ZFP36 could bind to adenylate uridylate-rich elements located in PRC1 mRNA 3′UTR to downregulate PRC1 expression. Taken together, our findings identified that ZFP36 regulated PRC1 to exert anti-tumor effect, which suggested a potential therapeutic strategy for treating HCC by exploiting ZFP36/PRC1 axis.
Highlights
The epithelial–mesenchymal transition (EMT) is a process used during normal wound healing and stem cell regulation that is synonymous with the progression of cancer (Lamouille et al, 2014)
ZFP36 was downregulated while Protein regulator of cytokinesis 1 (PRC1) was upregulated in matched Hepatocellular carcinoma (HCC) than adjacent normal tissue acquired from 35 patients by qRT-PCR (Figures 1A,B) and western blotting analysis (Figures 1D–F)
Resistance to chemotherapy in liver cancers, such as HCC, is believed to be a synergistic interaction that involves at least 100 different genes, which are stimulated by pharmacological treatment (Tian et al, 2014; Ceballos et al, 2018; Marin et al, 2018)
Summary
The epithelial–mesenchymal transition (EMT) is a process used during normal wound healing and stem cell regulation that is synonymous with the progression of cancer (Lamouille et al, 2014). The induction of motile mesenchymal cells is initiated by the dissolution of epithelial cell–cell junctions followed by a change of cellular polarity and the reorganization of the cytoskeleton (Kalluri and Weinberg, 2009). The loss of E-cadherin, which is expressed at high levels in epithelial cells, is considered fundamental to the progression of EMT (Beavon, 2000). During hepatic tumor progression, ZFP36 acted as tumorsuppressor by inhibiting cell proliferation and migration, and slightly increasing chemosensitivity to doxorubicin and sorafénib (Krohler et al, 2019). The underlying molecular mechanism by which ZFP36 inhibits tumor growth in HCC progression remains unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
