Down-regulation in human cancers of DRHC, a novel helicase-like gene from 17q25.1 that inhibits cell growth

Nagai, Hisaki; Yabe, Aya; Mine, Nobuya; Mikami, Iwao; Fujiwara, Hiromichi; Terada, Yayoi; Hirano, Akira; Tsuneizumi, Michiko; Yokota, Takashi; Emi, Mitsuru

doi:10.1016/s0304383502006882

Cited by 7 publications

(6 citation statements)

References 12 publications

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“…However, this was based on semi-quantitative RT-PCR analysis of HELZ expression in 95 tumor cell lines and the observation that exogenous HELZ expression inhibited proliferation and colony formation of hepatoma cells in vitro [49]. Contrary, the only functional HELZ data published so far suggest an adaptory role for HELZ linking the histone methyltransferase Smyd3 to RNA polymerase II, thereby transactivating oncogenes, homeobox genes and cell cycle regulators [8].…”

Section: Discussionmentioning

confidence: 99%

The Putative RNA Helicase HELZ Promotes Cell Proliferation, Translation Initiation and Ribosomal Protein S6 Phosphorylation

Hasgall

Hoogewijs²,

Faza³

et al. 2011

PLoS ONE

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The hypoxia–inducible transcription factor (HIF) is a key component of the cellular adaptation mechanisms to hypoxic conditions. HIFα subunits are degraded by prolyl-4-hydroxylase domain (PHD) enzyme-dependent prolyl-4-hydroxylation of LxxLAP motifs that confer oxygen-dependent proteolytic degradation. Interestingly, only three non-HIFα proteins contain two conserved LxxLAP motifs, including the putative RNA helicase with a zinc finger domain HELZ. However, HELZ proteolytic regulation was found to be oxygen-independent, supporting the notion that a LxxLAP sequence motif alone is not sufficient for oxygen-dependent protein destruction. Since biochemical pathways involving RNA often require RNA helicases to modulate RNA structure and activity, we used luciferase reporter gene constructs and metabolic labeling to demonstrate that HELZ overexpression activates global protein translation whereas RNA-interference mediated HELZ suppression had the opposite effect. Although HELZ interacted with the poly(A)-binding protein (PABP) via its PAM2 motif, PABP was dispensable for HELZ function in protein translation. Importantly, downregulation of HELZ reduced translational initiation, resulting in the disassembly of polysomes, in a reduction of cell proliferation and hypophosphorylation of ribosomal protein S6.

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Section: Discussionmentioning

confidence: 99%

The Putative RNA Helicase HELZ Promotes Cell Proliferation, Translation Initiation and Ribosomal Protein S6 Phosphorylation

Hasgall

Hoogewijs²,

Faza³

et al. 2011

PLoS ONE

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“…The HELZ and SRPK3 mutations were present in both the recurrence and the primary tumor, but the other mutations were specific to the recurrence sample. HELZ is a member of the superfamily I of RNA helicases [12] and has been suggested to have a tumor suppressive role in a variety of cancers [13]. SRPK3 is a serine/threonine kinase required for normal muscular differentiation [14].…”

Section: Single Nucleotide Variants and Insertion/deletionsmentioning

confidence: 99%

Diagnostic Value of Next-Generation Sequencing in an Unusual Sphenoid Tumor

Jamshidi

Pleasance

et al. 2014

The Oncologist

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Extraordinary advancements in sequencing technology have made what was once a decade-long multi-institutional endeavor into a methodology with the potential for practical use in a clinical setting.We therefore set out to examine the clinical value of next-generation sequencing by enrolling patients with incurable or ambiguous tumors into the Personalized OncoGenomics initiative at the British Columbia Cancer Agency whereby whole genome and transcriptome analyses of tumor/ normal tissue pairs are completed with the ultimate goal of directing therapeutics. First, we established that the sequencing, analysis, and communication with oncologists could be completed in less than 5 weeks. Second, we found that cancer diagnostics is an area that can greatly benefit from the comprehensiveness of a whole genome analysis. Here, we present a scenario in which a metastasized sphenoid mass, which was initially thought of as an undifferentiated squamous cell carcinoma, was rediagnosed as an SMARCB1-negative rhabdoid tumor based on the newly acquired finding of homozygous SMARCB1 deletion. The new diagnosis led to a change in chemotherapy and a complete nodal response in the patient. This study also provides additional insight into the mutational landscapeof an adult SMARCB1-negative tumor that has not been explored at a whole genome and transcriptome level. The Oncologist 2014;19:623-630Implications for Practice: We show that use of next-generation sequencing in clinical settings is practical and can benefit patients because of the ability to define tumors genetically.

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“…5C; 1-0-14 ). HELZ has differential influence in cancer, acting as a tumor suppressor or oncogene [61-64]. UPF1 downregulation is associated with poor prognosis in gastric cancer and hepatocellular carcinoma, and mutations often occur in pancreatic adenosquamous carcinoma [65-67].…”

Section: Resultsmentioning

confidence: 99%

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

Santos

Icyuz

Pound

et al. 2019

Preprint

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10Knowledge about synthetic lethality can be applied to enhance the efficacy of 11 anti-cancer therapies in individual patients harboring genetic alterations in their cancer 12 that specifically render it vulnerable. We investigated the potential for high-resolution 13 phenomic analysis in yeast to predict such genetic vulnerabilities by systematic, 14 comprehensive, and quantitative assessment of drug-gene interaction for gemcitabine 15 and cytarabine, substrates of deoxycytidine kinase that have similar molecular structures 16 yet distinct anti-tumor efficacy. Human deoxycytidine kinase (dCK) was conditionally 17 expressed in the S. cerevisiae genomic library of knockout and knockdown (YKO/KD) 18 strains, to globally and quantitatively characterize differential drug-gene interaction for 19 gemcitabine and cytarabine. Pathway enrichment analysis revealed that autophagy, 20 histone modification, chromatin remodeling, and apoptosis-related processes influence 21 gemcitabine specifically, while drug-gene interaction specific to cytarabine was less 22 enriched in Gene Ontology. Processes having influence over both drugs were DNA 23 repair and integrity checkpoints and vesicle transport and fusion. Non-GO-enriched 24 genes were also informative. Yeast phenomic and cancer cell line pharmacogenomics 25 data were integrated to identify yeast-human homologs with correlated differential gene 26 2 expression and drug-efficacy, thus providing a unique resource to predict whether 27 differential gene expression observed in cancer genetic profiles are causal in tumor-28 specific responses to cytotoxic agents. 29 30 Keywords: 31 yeast phenomics, gene-drug interaction, genetic buffering, quantitative high 32 throughput cell array phenotyping (Q-HTCP), cell proliferation parameters (CPPs), 33 gemcitabine, cytarabine, recursive expectation-maximization clustering (REMc), 34 pharmacogenomics 35 36 Introduction: 37Genomics has enabled targeted therapy aimed at cancer driver genes and 38 oncogenic addiction [1], yet traditional cytotoxic chemotherapeutic agents remain among 39 the most widely used and efficacious anti-cancer therapies [2]. Changes in the genetic 40 network underlying cancer can produce vulnerabilities to cytotoxic chemotherapy that 41 further influence the therapeutic window and provide additional insight into their 42 mechanisms of action [3,4]. A potential advantage of so-called synthetic lethality-based 43 treatment strategies is that they could have efficacy against passenger gene mutation or 44 compensatory gene expression, while classic targeted therapies are directed primarily at 45 driver genes ( Fig. 1A). Quantitative high throughput cell array phenotyping of the yeast 46 knockout and knockdown libraries provides a phenomic means for systems level, high- 47resolution modeling of gene interaction [5][6][7][8][9], which is applied here to predict cancer-48 relevant drug-gene interaction through integration with cancer pharmacogenomics 49 resources ( Fig. 1B). 50Nucleoside analogs include a diverse group of co...

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Down-regulation in human cancers of DRHC, a novel helicase-like gene from 17q25.1 that inhibits cell growth

Cited by 7 publications

References 12 publications

The Putative RNA Helicase HELZ Promotes Cell Proliferation, Translation Initiation and Ribosomal Protein S6 Phosphorylation

The Putative RNA Helicase HELZ Promotes Cell Proliferation, Translation Initiation and Ribosomal Protein S6 Phosphorylation

Diagnostic Value of Next-Generation Sequencing in an Unusual Sphenoid Tumor

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

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