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FUT3-dependent DDX21 fucosylation links elevated CA19-9 to pancreatic cancer metastasis via MIB2 alternative splicing and E-cadherin destabilization

ABSTRACT: Elevated carbohydrate antigen 19-9 (CA19-9) is strongly associated with distant metastasis and poor prognosis in pancreatic ductal adenocarcinoma (PDAC), yet the underlying mechanisms remain unclear. In this study, we investigated a FUT3-dependent glycosylation–splicing regulatory mechanism involved in pancreatic cancer metastasis. RNA sequencing was performed in BxPC-3 pancreatic cancer cells with DDX21 overexpression and corresponding vector controls to characterize DDX21-dependent transcriptional and alternative splicing changes. Integrated analyses identified MIB2 exon 8 skipping as a functionally relevant downstream event associated with E-cadherin destabilization and metastatic phenotypes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE346317 | GEO | 2026/09/12

REPOSITORIES: GEO

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FUT3-dependent DDX21 fucosylation links elevated CA19-9 to pancreatic cancer metastasis via MIB2 alternative splicing and E-cadherin destabilization

Project description:FUT3-dependent DDX21 fucosylation links elevated CA19-9 to pancreatic cancer metastasis via MIB2 alternative splicing and E-cadherin destabilization

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Glucose dissociates DDX21 dimers to regulate mRNA splicing and promote epidermal differentiation

Project description:We discovered that glucose directly bind to DDX21, induced the conformation change of the proteins and inhibit its helicase activity. Glucose also inhibits the dimerization of DDX21, re-localize DDX21 from nucleolus to nucleoplasm and reassemble DDX21 to RNA splicing complex. DDX21 is essential for epidermal differentiation while with normal glucose condition, DDX21 was re-localized from nucleolus to nucleoplasm, bind to splicing factors and mRNA introns more to regulate splicing of key differentiation factors and promote epidermal differentiation.

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RNA helicase DDX21 coordinates transcription and noncoding RNA processing of the ribosomal pathway

Project description:DEAD-box RNA helicases are vital for the regulation of various aspects of the RNA life cycle, but the molecular underpinnings of their involvement, particularly in mammalian cells, remain poorly understood. Here we show that the DEAD-box RNA helicase DDX21 can sense transcriptional status of both RNA Pol I and Pol II to control transcriptional and post-transcriptional steps of ribosome biogenesis in human cells. We demonstrate that DDX21 widely associates with Pol I- and Pol II-transcribed genes and with diverse species of protein-coding and noncoding RNAs. Although broad, these molecular interactions, both at the chromatin and at the RNA level, exhibit a remarkable specificity for the ribosomal pathway. In the nucleolus, DDX21 occupies the transcribed rDNA locus, directly contacts both rRNA and snoRNAs and, as a functional component of the snoRNA ribonucleoprotein (snoRNP) complex, promotes modification of rRNA. In the nucleoplasm, DDX21 is incorporated into the 7SK snRNP complex, which facilitates DDX21 association with promoters of Pol II-transcribed genes encoding ribosomal proteins and snoRNAs. Promoter-bound DDX21 facilitates the release of P-TEFb from the 7SK snRNP, enhancing productive Pol II elongation. Altogether, we present a unifying mechanism for the coordinated regulation of ribosomal genes across nuclear compartments, and provide first evidence implicating a mammalian RNA helicase in RNA modification and Pol II elongation control. Examination of DDX21 chromatin association and DDX21 RNA interacting partners in HEK293 cells

2014-11-17 | E-GEOD-56802 | biostudies-arrayexpress

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