Abstract
EIF4A3, a member of the DEAD-box protein family, is a nuclear matrix protein and a core component of the exon junction complex (EJC). Under physiological conditions, EIF4A3 participates in post-transcriptional gene regulation by promoting EJC control of precursor mRNA splicing, thus influencing nonsense-mediated mRNA decay. In addition, EIF4A3 maintains the expression of significant selenoproteins, including phospholipid hydroperoxide glutathione peroxidase and thioredoxin reductase 1. Several recent studies have shown that EIF4A3 promotes tumor growth in multiple human cancers such as glioblastoma, hepatocellular carcinoma, pancreatic cancer, and ovarian cancer. Molecular biology studies also showed that EIF4A3 is recruited by long non-coding RNAs to regulate the expression of certain proteins in tumors. However, its tumor-related functions and underlying mechanisms are not well understood. Here, we review the physiological role of EIF4A3 and the potential association between EIF4A3 overexpression and tumorigenesis. We also evaluate the protein’s potential utility as a diagnosis biomarker, therapeutic target, and prognosis indicator, hoping to provide new ideas for future research.
Highlights
DEAD-box helicases are a family of adenosine triphosphate (ATP)-dependent RNA helicases belonging to the RNA helicase superfamily II
That study showed that when the expression of Eukaryotic initiation factor 4A-3 (EIF4A3), LINC00680, and TTNAS1 was downregulated in PANC-1 and SW1990 cells, their proliferation, migration, and invasion was impaired, while tumor growth was inhibited in vivo and glioblastoma cell apoptosis was promoted
Further experiments showed that LINC01232 reduced the stability of transmembrane 9 superfamily member 2 (TM9SF2) mRNA, while EIF4A3 upregulation had the opposite effect. These results suggest that EIF4A3 may contribute to pancreatic adenocarcinoma (PAAD) progression by stabilizing TM9SF2 mRNA
Summary
DEAD-box helicases are a family of adenosine triphosphate (ATP)-dependent RNA helicases belonging to the RNA helicase superfamily II. EIF4A3 is highly expressed in many tumors, such as glioblastoma, hepatocellular carcinoma (HCC), pancreatic cancer, and ovarian cancer, and it can be recruited by long non-coding RNAs (lncRNAs) to stabilize proteins and promote tumorigenesis. The interaction between EIF4A3 and lncRNAs plays a vital role in oncogenesis by participating in the post-transcriptional regulation of RNA, thereby affecting gene expression (Table 1).
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