DDX10 RNA Helicase: Structure, Function, and Oncogenic Roles Across Solid and Hematologic Tumors

TL;DR

This paper reviews the RNA helicase DDX10, its role in RNA metabolism, and its contribution to cancer development in various tumor types.

Contribution

The paper provides a comprehensive analysis of DDX10's structure, function, and oncogenic roles across multiple cancers.

Findings

DDX10 contributes to pre-rRNA processing and ribosome biogenesis, impacting cell proliferation.

Aberrant DDX10 expression is linked to tumor progression, therapy resistance, and poor prognosis.

The NUP98::DDX10 fusion in acute myeloid leukemia disrupts transcriptional regulation and promotes leukemogenesis.

Abstract

DEAD-box (DDX) RNA helicases are essential regulators of RNA metabolism and gene expression. Among them, DDX10 remains poorly characterized despite growing evidence supporting its involvement in human diseases. This review provides a comprehensive analysis of DDX10, from its structural and functional features to its emerging roles in solid tumors and hematologic malignancies. We discuss how DDX10, through its conserved domains, contributes to pre-rRNA processing, ribosome biogenesis, and cell proliferation, and explore potential links between DDX10 and processes such as liquid–liquid phase separation (LLPS) and epigenetic regulation, which may underlie its roles in cancer cell plasticity and stress response. We argue that the dysregulation of these fundamental cellular processes positions DDX10 as a focal point where aberrant RNA metabolism and altered molecular condensates converge to disrupt transcriptional homeostasis and drive oncogenic transformation. Aberrant DDX10 expression is a recurrent feature across multiple cancers, where it promotes tumor progression, therapy resistance, and poor prognosis. Moreover, DDX10 participates in oncogenic fusion events, most notably the NUP98::DDX10 fusion identified in a subset of acute myeloid leukemias, which drives leukemogenesis by disrupting transcriptional regulation and cellular differentiation. Given its tumor-associated expression and diverse biological functions, DDX10 is increasingly recognized as a potential diagnostic biomarker and a promising target for therapeutic strategies. By consolidating current knowledge under this unifying framework, this review highlights the multifaceted roles of DDX10 in cancer biology, advocating further research into its molecular functions and translational potential.

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