Abstract
NAP1L1 has been reported to be significantly involved in the carcinogenesis of hepatocellular carcinoma (HCC). Yet, its detailed molecular basis is still to be determined. Based on the analysis of The Cancer Genome Atlas (TCGA) database, NAP1L1 mRNA was found to be upregulated and predicted the poor prognosis initially. Subsequently, consistent with the prediction, the upregulated expression of NAP1L1 mRNA and protein levels was confirmed by quantitative polymerase chain reaction (qPCR), Western blot, and immunohistochemistry assays. Upregulated NAP1L1 protein positively promoted the disease progression and poor prognosis of HCC. In addition, NAP1L1 protein expression was considered as an independent prognostic factor in HCC. Inhibition of NAP1L1 expression by siRNA or shRNA pathway significantly reduced the cell proliferation and cell cycle transformation in vitro and in vivo. Mechanism analysis first showed that the function of NAP1L1 was to recruit hepatoma-derived growth factor (HDGF), an oncogene candidate widely documented in tumors. Furthermore, the latter interacted with c-Jun, a key oncogenic transcription factor that can induce the expression of cell cycle factors and thus stimulate the cell growth in HCC. Finally, transfecting HDGF or c-Jun could reverse the suppressive effects on HCC growth in NAP1L1-suppressed HCC cells. Our data indicate that NAP1L1 is a potential oncogene and acts via recruiting HDGF/c-Jun in HCC.
Highlights
Liver cancer is one of the leading causes of cancer-related deaths in the world (Akinyemiju et al, 2017), causing the fourth deaths in most common malignancy and the third deaths in leading tumor-related deaths in China
Hepatocellular carcinoma is a type of heterogeneous cancer with a lot of factors implicated in its development, with chronic infection and cirrhosis by hepatitis B virus (HBV) being the most prevalent (Beasley, 1988; McGlynn et al, 2015; Yamashita and Kaneko, 2016)
Consistent with the prediction, the upregulated expression of NAP1L1 mRNA and protein levels was confirmed by real-time quantitative PCR, Western blot analysis of the human hepatocellular carcinoma (HCC) and normal liver cell lines, and immunohistochemistry assay on the clinic human HCC tissue sections (Figures 1C–E)
Summary
Liver cancer is one of the leading causes of cancer-related deaths in the world (Akinyemiju et al, 2017), causing the fourth deaths in most common malignancy and the third deaths in leading tumor-related deaths in China. Cirrhosis due to metabolic dysfunction, excessive alcohol consumption, non-alcoholic fatty liver disease (NAFLD), and hepatitis C virus (HCV) infection are involved in HCC development (Venook et al, 2010; Morgan et al, 2013; Calzadilla and Adams, 2016; Yamashita and Kaneko, 2016). These factors alone or together lead to the imbalance of gene expression in the normal liver, inducing the occurrence and development of HCC (Lin et al, 2019, 2020; Liu et al, 2020)
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.
