The DEAD-box helicase DDX56 is a conserved stemness regulator in normal and cancer stem cells

Pryszlak, Michael; Wiggans, Mallory; Chen, Xin; Jaramillo, Julia E.; Burns, Sarah; Richards, Laura M.; Pugh, Trevor J.; Kaplan, David R.; Huang, Xi; Dirks, Peter B.; Pearson, Bret J.

doi:10.1016/j.celrep.2021.108903

Cited by 9 publications

(15 citation statements)

References 105 publications

(151 reference statements)

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“…DDX56 has also been reported to regulate ribosome assembly through its association with the Oct4 and Sox2 complex, which is necessary to maintain embryonic stem cells (ESCs) proliferation [ 91 ]. DDX56 is upregulated in osteosarcoma and colorectal cancer ( Table 1 ) [ 92 , 93 , 94 ]. Depletion of the DDX56 arrest cell cycle in the G2/M phase via the decrease of tumor suppressor WEE1 expression, which functions as a G2/M DNA damage checkpoint ( Figure 3 ) [ 94 ], results in the inhibition of cell proliferation and clone formation and the induction of p53 mediated apoptosis in osteosarcoma cells [ 92 , 93 ].…”

Section: The Role Of Rna Helicases In Regulation Of Cell Cycle Progressionmentioning

confidence: 99%

“…DDX56 is upregulated in osteosarcoma and colorectal cancer ( Table 1 ) [ 92 , 93 , 94 ]. Depletion of the DDX56 arrest cell cycle in the G2/M phase via the decrease of tumor suppressor WEE1 expression, which functions as a G2/M DNA damage checkpoint ( Figure 3 ) [ 94 ], results in the inhibition of cell proliferation and clone formation and the induction of p53 mediated apoptosis in osteosarcoma cells [ 92 , 93 ]. However, whether DDX56 regulates the cell cycle through p53-p21 signaling needs to be further investigated.…”

Section: The Role Of Rna Helicases In Regulation Of Cell Cycle Progressionmentioning

confidence: 99%

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DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

Zhang

2021

Cells

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Cell cycle is regulated through numerous signaling pathways that determine whether cells will proliferate, remain quiescent, arrest, or undergo apoptosis. Abnormal cell cycle regulation has been linked to many diseases. Thus, there is an urgent need to understand the diverse molecular mechanisms of how the cell cycle is controlled. RNA helicases constitute a large family of proteins with functions in all aspects of RNA metabolism, including unwinding or annealing of RNA molecules to regulate pre-mRNA, rRNA and miRNA processing, clamping protein complexes on RNA, or remodeling ribonucleoprotein complexes, to regulate gene expression. RNA helicases also regulate the activity of specific proteins through direct interaction. Abnormal expression of RNA helicases has been associated with different diseases, including cancer, neurological disorders, aging, and autosomal dominant polycystic kidney disease (ADPKD) via regulation of a diverse range of cellular processes such as cell proliferation, cell cycle arrest, and apoptosis. Recent studies showed that RNA helicases participate in the regulation of the cell cycle progression at each cell cycle phase, including G1-S transition, S phase, G2-M transition, mitosis, and cytokinesis. In this review, we discuss the essential roles and mechanisms of RNA helicases in the regulation of the cell cycle at different phases. For that, RNA helicases provide a rich source of targets for the development of therapeutic or prophylactic drugs. We also discuss the different targeting strategies against RNA helicases, the different types of compounds explored, the proposed inhibitory mechanisms of the compounds on specific RNA helicases, and the therapeutic potential of these compounds in the treatment of various disorders.

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Section: The Role Of Rna Helicases In Regulation Of Cell Cycle Progressionmentioning

confidence: 99%

Section: The Role Of Rna Helicases In Regulation Of Cell Cycle Progressionmentioning

confidence: 99%

DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

Zhang

2021

Cells

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“…The sample size of the patient models was relatively small in a single center. Although DDX56 is enriched primarily in the nucleolus, it disperses throughout the cytoplasm upon treatment with cytotoxic agents [ 42 ]. This phenotype predicts that DDX56 may have different functions in different cellular organelles.…”

Section: Discussionmentioning

confidence: 99%

DEAD-box helicase 56 functions as an oncogene promote cell proliferation and invasion in gastric cancer via the FOXO1/p21 Cip1/c-Myc signaling pathway

Wang

et al. 2022

Bioengineered

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DEAD-box helicase (DDX) family exerts a critical effect on cancer initiation and progression through alternative splicing, transcription and ribosome biogenesis. Increasing evidence has demonstrated that DEAD-box helicase 56 (DDX56) is over-expressed in several cancers, which plays an oncogenic role. Till the present, the impact of DDX56 on gastric cancer (GC) remains unclear. We conducted high-throughput sequencing (RNA-seq) to demonstrate aberrant DDX56 levels within 10 GC and matched non-carcinoma tissue samples. DDX56 levels were detected through qRT‐PCR, western blotting (WB) and immunochemical staining in GC patients. We conducted gain- and loss-of-function studies to examine DDX56’s biological role in GC development. In vitro, we carried out 5‑Ethynyl‑2‑deoxyuridine (EdU), scratch, Transwell, and flow cytometry (FCM) assays for detecting GC cell growth, invasion, migration and apoptosis. Additionally, gene set enrichment analysis (GSEA), WB assay, and Encyclopedia of RNA Interactomes (ENCORI) were carried out for analyzing DDX56-regulated downstream genes and signaling pathways. In vivo, tumor xenograft experiment was performed for investigating how DDX56 affected GC development within BALB/c nude mice. Functionally, DDX56 knockdown arrested cell cycle at G1 phase, invasion and migration of AGS and MKN28 cells, and enhanced their apoptosis. Ectopic DDX56 expression enhanced the cell growth, migration and invasion, and inhibited apoptosis. Knockdown of DDX56 suppressed GC growth in the tumor models of BALB/c nude mice. Mechanistically, DDX56 post-transcriptionally suppressed FOXO1/p21 Cip1 protein expression, which could activate its downstream cyclin E1/CDK2/c-Myc signaling pathways. This sheds lights on the GC pathogenic mechanism and offers a potential anti-cancer therapeutic target.

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“…The DDX family contains 12 highly conserved motifs and can be easily identified by the inclusion of special DEAD (ASP-Glu-Ala-ASP) motifs. These highly conserved DDX RNA helicases are necessary for almost all aspects of the RNA metabolism process, from RNA transcription to degradation [6][7][8][9]. Recently, emerging evidence has showed that DDX helicases can act as sensors, regulators and/or effectors during viral infections [10,11], implicating the diverse roles of these DDX helicases.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Identification and Characterization of the Soybean DEAD-Box Gene Family and Expression Response to Rhizobia

Wang

Liao

et al. 2022

IJMS

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DEAD-box proteins are a large family of RNA helicases that play important roles in almost all cellular RNA processes in model plants. However, little is known about this family of proteins in crops such as soybean. Here, we identified 80 DEAD-box family genes in the Glycine max (soybean) genome. These DEAD-box genes were distributed on 19 chromosomes, and some genes were clustered together. The majority of DEAD-box family proteins were highly conserved in Arabidopsis and soybean, but Glyma.08G231300 and Glyma.14G115100 were specific to soybean. The promoters of these DEAD-box genes share cis-acting elements involved in plant responses to MeJA, salicylic acid (SA), low temperature and biotic as well as abiotic stresses; interestingly, half of the genes contain nodulation-related cis elements in their promoters. Microarray data analysis revealed that the DEAD-box genes were differentially expressed in the root and nodule. Notably, 31 genes were induced by rhizobia and/or were highly expressed in the nodule. Real-time quantitative PCR analysis validated the expression patterns of some DEAD-box genes, and among them, Glyma.08G231300 and Glyma.14G115100 were induced by rhizobia in root hair. Thus, we provide a comprehensive view of the DEAD-box family genes in soybean and highlight the crucial role of these genes in symbiotic nodulation.

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The DEAD-box helicase DDX56 is a conserved stemness regulator in normal and cancer stem cells

Cited by 9 publications

References 105 publications

DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

DEAD-box helicase 56 functions as an oncogene promote cell proliferation and invasion in gastric cancer via the FOXO1/p21 Cip1/c-Myc signaling pathway

Genome-Wide Identification and Characterization of the Soybean DEAD-Box Gene Family and Expression Response to Rhizobia

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