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

**Authors:** Giorgia Isinelli, Genny Scacci, Arianna Capocchia, Carla Emiliani, Cristina Mecucci, Roberta La Starza, Danika Di Giacomo

PMC · DOI: 10.3390/genes17020138 · 2026-01-27

## 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.

## Key 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.

## Linked entities

- **Genes:** DDX10 (DEAD-box helicase 10) [NCBI Gene 1662], NUP98 (nucleoporin 98 and 96 precursor) [NCBI Gene 4928]
- **Proteins:** DDX10 (DEAD-box helicase 10)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, SRSF1 (serine and arginine rich splicing factor 1) [NCBI Gene 6426] {aka ASF, NEDFBA, SF2, SF2p33, SFRS1, SRp30a}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}, ATF4 (activating transcription factor 4) [NCBI Gene 468] {aka CREB-2, CREB2, TAXREB67, TXREB}, NUP98 (nucleoporin 98 and 96 precursor) [NCBI Gene 4928] {aka ADIR2, NUP196, NUP96, Nup98-96}, RPL35 (ribosomal protein L35) [NCBI Gene 11224] {aka DBA19, L35, uL29}, Ddx10 (DEAD box helicase 10) [NCBI Gene 77591] {aka 4632415A01Rik}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, ATG10 (autophagy related 10) [NCBI Gene 83734] {aka APG10, APG10L, ATG10S, pp12616}, HFM1 (helicase for meiosis 1) [NCBI Gene 164045] {aka MER3, POF9, SEC63D1, Si-11, Si-11-6, helicase}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, IMP4 (IMP U3 small nucleolar ribonucleoprotein 4) [NCBI Gene 92856] {aka BXDC4}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, FBL (fibrillarin rRNA 2'-O-methyltransferase) [NCBI Gene 2091] {aka FIB, FLRN, Nop1, RNU3IP1}, CD34 (CD34 molecule) [NCBI Gene 947], SKA3 (spindle and kinetochore associated complex subunit 3) [NCBI Gene 221150] {aka C13orf3, RAMA1}, AKR1C3 (aldo-keto reductase family 1 member C3) [NCBI Gene 8644] {aka DD3, DDX, HA1753, HAKRB, HAKRe, HSD17B5}, HCA4 (RNA-dependent ATPase HCA4) [NCBI Gene 853419] {aka DBP4, ECM24}, RAB27B (RAB27B, member RAS oncogene family) [NCBI Gene 5874] {aka C25KG}, DDX10 (DEAD-box helicase 10) [NCBI Gene 1662] {aka Dbp4, HRH-J8}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PROM1 (prominin 1) [NCBI Gene 8842] {aka AC133, CD133, CORD12, MCDR2, MSTP061, PROML1}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, RAD51 (RAD51 recombinase) [NCBI Gene 5888] {aka BRCC5, FANCR, HRAD51, HsRad51, HsT16930, MRMV2}, NOL10 (nucleolar protein 10) [NCBI Gene 79954] {aka PQBP5}, VIM (vimentin) [NCBI Gene 7431], DDX56 (DEAD-box helicase 56) [NCBI Gene 54606] {aka DDX21, DDX26, NOH61}
- **Diseases:** ovarian cancer (MESH:D010051), II and III (MESH:C536044), breast cancer (MESH:D001943), CMML (MESH:D054429), bladder cancer (MESH:D001749), chronic myelomonocytic leukemia (MESH:D015477), DLBCL (MESH:D016403), CRC (MESH:D015179), leukemia (MESH:D007938), hematologic disorders (MESH:D006402), tumorigenic (MESH:D002471), hormone receptor-negative (MESH:D046150), acute leukemia of ambiguous lineage not otherwise specified (MESH:D015456), Philadelphia-like B-lineage acute lymphoblastic leukemia (MESH:D054198), infection (MESH:D007239), tumorigenesis (MESH:D063646), gastric cancer (MESH:D013274), LUAD (MESH:D000077192), MPM (MESH:D000086002), OSCC (MESH:D000077195), LLPS (MESH:D000210), Solid and Hematologic Tumors (MESH:D019337), MDS (MESH:D009190), AML (MESH:D015470), pancreatic cancer (MESH:D010190), glioma (MESH:D005910), melanoma (MESH:D008545), prostate cancer (MESH:D011471), injury to (MESH:D014947), PDAC (MESH:D021441), osteosarcoma (MESH:D012516), primary pigmented papillary epithelial tumor of the sella (MESH:D002277), AP-CML (MESH:D015464), cancers (MESH:D009369), lung cancer (MESH:D008175)
- **Chemicals:** 3-MA (-), selenium (MESH:D012643), serine (MESH:D012694), amino acid (MESH:D000596), 1,6-hexanediol (MESH:C027765), adenine (MESH:D000225), inorganic phosphate (MESH:D010710), Pi (MESH:D010716), ADP (MESH:D000244)
- **Species:** Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus 1 (no rank) [taxon 11676], Porcine reproductive and respiratory syndrome virus (no rank) [taxon 28344], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** p.Asp788del, Phe-Gly, p.Arg509Cys
- **Cell lines:** MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), hCD34 — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_ZX24), NCI-H460 — Homo sapiens (Human), Lung large cell carcinoma, Cancer cell line (CVCL_0459), MG63 — Homo sapiens (Human), Osteosarcoma, Cancer cell line (CVCL_0426), MCF7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940211/full.md

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Source: https://tomesphere.com/paper/PMC12940211