Abstract
DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-Linked (DDX3X), also known as DDX3, is one of the most widely studied and evolutionarily conserved members of the DEAD-box RNA helicase subfamily, and has been reported to participate in several cytosolic steps of mRNA metabolism. DDX3X facilitates the translation of specific targets via its helicase activity and regulates factors of the translation initiation complex. Emerging evidence illustrates the biological activities of DDX3X beyond its originally identified functions. The nonconventional regulatory effects include acting as a signaling adaptor molecule independent of enzymatic RNA remodeling, and DDX3X exhibits abnormal expression in cancers. DDX3X interacts with specific components to perform both oncogenic and tumor-suppressive roles in modulating tumor proliferation, migration, invasion, drug resistance, and cancer stemness in many types of cancers, indicating the need to unravel the associated molecular mechanisms. In this review article, we summarized and integrated current findings relevant to DDX3X in cancer research fields, cytokines and compounds modulating DDX3X’s functions, and the released transcriptomic information and cancer patient clinical data from public databases. We found evidence for DDX3X having multiple impacts on cancer progression, and evaluated DDX3X expression levels in a pancancer panel and its associations with patient survival in each cancer-type cohort.
Highlights
DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-Linked (DDX3X) is a member of the DEAD-box family of RNA helicases and has been reported to be involved in double-stranded RNA unwinding [1], pre-mRNA splicing [2], RNA export [3], transcription [4], and translation [5,6,7]
A recent report further showed that a systematic affinity proteomics approach identified several high-confidence interactors, including DDX3X, which could assemble into the rG4 located in the 5 -untranslated region (UTR) of the NRAS oncogene transcript
We summarized and integrated published references and data from an in silico analysis to clarify the relative expression levels of DDX3X in multiple types of cancers
Summary
DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-Linked (DDX3X) is a member of the DEAD-box family of RNA helicases and has been reported to be involved in double-stranded RNA unwinding [1], pre-mRNA splicing [2], RNA export [3], transcription [4], and translation [5,6,7]. Due to its complicated function in RNA metabolism, DDX3X has gained increasing attention for its biological functions in various types of cancers and has been shown to modulate cancer progression in a complex manner This complexity was further increased by evidence revealing that DEAD box proteins generally do not function alone but instead act as components of multiprotein complexes [16]. The interaction of 5 -UTR rG4-containing transcripts was decreased upon mutation of the DDX3X glycine-arginine (GAR) domain [19]. Both tumor-promotive and tumor-suppressive effects of DDX3X have been identified and reported. We focus on the biological function of DDX3X in cancer, and further illustrate its clinical significance on a pancancer scale
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