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Review
. 2018 Jul 27;50(7):1-12.
doi: 10.1038/s12276-018-0106-1.

ARD1/NAA10 in hepatocellular carcinoma: pathways and clinical implications

Danbi Lee  1 , Myoung-Kuk Jang  2 , Ji Hae Seo  3 , Soo Hyung Ryu  4 , Jeong A Kim  5 , Young-Hwa Chung  6
Affiliations
Review

ARD1/NAA10 in hepatocellular carcinoma: pathways and clinical implications

Danbi Lee et al. Exp Mol Med. .

Abstract

Hepatocellular carcinoma (HCC), a representative example of a malignancy with a poor prognosis, is characterized by high mortality because it is typically in an advanced stage at diagnosis and leaves very little hepatic functional reserve. Despite advances in medical and surgical techniques, there is no omnipotent tool that can diagnose HCC early and then cure it medically or surgically. Several recent studies have shown that a variety of pathways are involved in the development, growth, and even metastasis of HCC. Among a variety of cytokines or molecules, some investigators have suggested that arrest-defective 1 (ARD1), an acetyltransferase, plays a key role in the development of malignancies. Although ARD1 is thought to be centrally involved in the cell cycle, cell migration, apoptosis, differentiation, and proliferation, the role of ARD1 and its potential mechanistic involvement in HCC remain unclear. Here, we review the present literature on ARD1. First, we provide an overview of the essential structure, functions, and molecular mechanisms or pathways of ARD1 in HCC. Next, we discuss potential clinical implications and perspectives. We hope that, by providing new insights into ARD1, this review will help to guide the next steps in the development of markers for the early detection and prognosis of HCC.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. The structure of ARD1.
a Structures of ARD1 isoforms. The ARD1235 and ARD1225 isoforms share a highly conserved N-acetyltransferase domain located between amino acids 45 and 130 (aa 45–130). The N-acetyltransferase domain contains an acetyl-CoA-binding site (RRLGLA) located at aa 82–87 and a nuclear localization signal (NLS) (KRSHRR) located at aa 78–83. ARD1235 and ARD1225 have completely different amino acid sequences in their C-terminal region, starting at aa 158. b Alternative splicing of ARD1 mRNA. ARD1 variants are derived from alternative RNA splicing. Alternative splicing at exon 8 alters the reading frame and introduces stop codons at amino acids 235 and 225, resulting in the production of two ARD1 isoforms, ARD1235 and ARD1225, respectively
Fig. 2
Fig. 2. Controversial roles of ARD1 in cancer development and progression.
Many studies have reported an important role of ARD1 in cancer progression. However, it is still debated whether human ARD1 serves as an oncogene or a tumor suppressor
See this image and copyright information in PMC

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References

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