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DKC1: a robust prognostic factor and potential therapeutic target in Multiple Myeloma

ABSTRACT: Multiple Myeloma (MM) is an incurable plasma cell malignancy. Dyskerin pseudouridine synthase 1 (DKC1), a nucleolar protein, is essential for RNA modification and cellular homeostasis, yet its role in MM remains unclear. Here, we report that elevated DKC1 expression independently predicted poor outcomes in MM and further refined prognostic stratification beyond the ISS system. Functional assays showed that DKC1 promoted MM cell proliferation, survival, and colony formation, whereas DKC1 knockdown or pharmacological inhibition of DKC1 by pyrazofurin inhibited proliferation and colonies, induced apoptosis, and suppressed tumor growth in xenografts. Mechanistically, DKC1 promotes tumor progression by stabilizing ATF5 mRNA through pseudouridylation, a direct post-transcriptional mechanism evidenced by site-specific pseudouridine mapping. Together, these findings highlight DKC1 as both a critical prognostic biomarker and a promising therapeutic target.

ORGANISM(S): Homo sapiens

PROVIDER: GSE308784 | GEO | 2026/04/15

REPOSITORIES: GEO

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Co-transcriptional pseudouridylation of mRNAs by the H/ACA complex controls translational efficiency [iCLIP]

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Genome-wide RNAi Screening Identifies pseudouridine synthase DKC1 promotes CRC proliferation through regulating ribosomal proteins expression

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