Expression of Noncoding Vault RNA in Human Malignant Cells and Its Importance in Mitoxantrone Resistance

Gopinath, Subash C.B.; Wadhwa, Renu; Kumar, Penmetcha K. R.

doi:10.1158/1541-7786.mcr-10-0242

Cited by 55 publications

(64 citation statements)

References 27 publications

(38 reference statements)

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“…Down-regulation of BACH1 in human acute myeloid leukemia cells decreases the cytotoxic effect of the anticancer drug cytosine arabinoside, rendering functional up-regulation of BACH1 a potential strategy for antileukemic therapy (11). In this respect, we have identified here two noncoding vault RNAs as BACH1 targets whose expression has been linked to Mitoxantrone resistance in human malignant cells (74). Further studies have to be carried out on these and other disease-relevant BACH1 targets.…”

Section: Discussionmentioning

confidence: 88%

The BTB and CNC Homology 1 (BACH1) Target Genes Are Involved in the Oxidative Stress Response and in Control of the Cell Cycle

Warnatz

Schmidt

Manke

et al. 2011

Journal of Biological Chemistry

142

134

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The regulation of gene expression in response to environmental signals and metabolic imbalances is a key step in maintaining cellular homeostasis. BTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements at low intracellular heme levels. Upon heme binding, BACH1 is released from the MAF recognition elements, resulting in increased expression of antioxidant response genes. To systematically address the gene regulatory networks involving BACH1, we combined chromatin immunoprecipitation sequencing analysis of BACH1 target genes in HEK 293 cells with knockdown of BACH1 using three independent types of small interfering RNAs followed by transcriptome profiling using microarrays. The 59 BACH1 target genes identified by chromatin immunoprecipitation sequencing were found highly enriched in genes showing expression changes after BACH1 knockdown, demonstrating the impact of BACH1 repression on transcription. In addition to known and new BACH1 targets involved in heme degradation (HMOX1, FTL, FTH1, ME1, and SLC48A1) and redox regulation (GCLC, GCLM, and SLC7A11), we also discovered BACH1 target genes affecting cell cycle and apoptosis pathways (ITPR2, CALM1, SQSTM1, TFE3, EWSR1, CDK6, BCL2L11, and MAFG) as well as subcellular transport processes (CLSTN1, PSAP, MAPT, and vault RNA). The newly identified impact of BACH1 on genes involved in neurodegenerative processes and proliferation provides an interesting basis for future dissection of BACH1-mediated gene repression in neurodegeneration and virus-induced cancerogenesis.

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Section: Discussionmentioning

confidence: 88%

The BTB and CNC Homology 1 (BACH1) Target Genes Are Involved in the Oxidative Stress Response and in Control of the Cell Cycle

Warnatz

Schmidt

Manke

et al. 2011

Journal of Biological Chemistry

142

134

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“…Processing is Drosha-independent and Dicer-dependent. svRNAs assemble with Ago proteins and guide sequence-specific cleavage of target mRNAs in a manner similar to miRNAs (Persson et al, 2009; Gopinath et al, 2010). Based on the similarities between svRNA- and miRNA-based degradation mechanisms, Rovira and colleagues identified several hundred mRNAs as predicted svRNA targets.…”

Section: Noncoding Rnas In Mrna Degradationmentioning

confidence: 99%

The regulation of mRNA stability in mammalian cells: 2.0

Brewer

2012

Gene

204

195

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Messenger RNA decay is an essential step in gene expression to set mRNA abundance in the cytoplasm. The binding of proteins and/or noncoding RNAs to specific recognition sequences or secondary structures within mRNAs dictates mRNA decay rates by recruiting specific enzyme complexes that perform the destruction processes. Often, the cell coordinates the degradation or stabilization of functional subsets of mRNAs encoding proteins collectively required for a biological process. As well, extrinsic or intrinsic stimuli activate signal transduction pathways that modify the mRNA decay machinery with consequent effects on decay rates and mRNA abundance. This review is an update to our 2001 Gene review on mRNA stability in mammalian cells, and we survey the enormous progress made over the past decade.

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“…The non-coding vault RNAs (vRNAs) are implicated in cancer cell resistance to chemotherapeutic exposure (Gopinath et al, 2005, 2010). vRNAs are components of large ribonucleoprotein vault particles that collectively participate in intracellular and nucleocytoplasmic transport as well as the extrusion of xenobiotics from nuclei of resistant cancer cells.…”

Section: Neuroactive Pharmacological Agents: Mirnas Regulate Drug mentioning

confidence: 99%

“…vRNAs are components of large ribonucleoprotein vault particles that collectively participate in intracellular and nucleocytoplasmic transport as well as the extrusion of xenobiotics from nuclei of resistant cancer cells. vRNAs directly bind mitoxantrone (Gopinath et al, 2005), and human glioblastoma, leukemia, and osteocarcinoma cell lines overexpress vRNA and exhibit higher resistance toward mitoxantrone treatment (Gopinath et al, 2010). vRNAs fold into secondary structures resembling miRNA precursors and give rise to small vRNAs (svRNAs) via a mechanism independent of Drosha but dependent on Dicer activity (Persson et al, 2009).…”

Section: Neuroactive Pharmacological Agents: Mirnas Regulate Drug mentioning

confidence: 99%

Non-coding RNAs—Novel targets in neurotoxicity

Tal

Tanguay

2012

NeuroToxicology

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Over the past ten years non-coding RNAs (ncRNAs) have emerged as pivotal players in fundamental physiological and cellular processes and have been increasingly implicated in cancer, immune disorders, and cardiovascular, neurodegenerative, and metabolic diseases. MicroRNAs (miRNAs) represent a class of ncRNA molecules that function as negative regulators of post-transcriptional gene expression. miRNAs are predicted to regulate 60% of all human protein-coding genes and as such, play key roles in cellular and developmental processes, human health, and disease. Relative to counterparts that lack bindings sites for miRNAs, genes encoding proteins that are post-transcriptionally regulated by miRNAs are twice as likely to be sensitive to environmental chemical exposure. Not surprisingly, miRNAs have been recognized as targets or effectors of nervous system, developmental, hepatic, and carcinogenic toxicants, and have been identified as putative regulators of phase I xenobiotic-metabolizing enzymes. In this review, we give an overview of the types of ncRNAs and highlight their roles in neurodevelopment, neurological disease, activity-dependent signaling, and drug metabolism. We then delve into specific examples that illustrate their importance as mediators, effectors, or adaptive agents of neurotoxicants or neuroactive pharmaceutical compounds. Finally, we identify a number of outstanding questions regarding ncRNAs and neurotoxicity.

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Expression of Noncoding Vault RNA in Human Malignant Cells and Its Importance in Mitoxantrone Resistance

Cited by 55 publications

References 27 publications

The BTB and CNC Homology 1 (BACH1) Target Genes Are Involved in the Oxidative Stress Response and in Control of the Cell Cycle

The BTB and CNC Homology 1 (BACH1) Target Genes Are Involved in the Oxidative Stress Response and in Control of the Cell Cycle

The regulation of mRNA stability in mammalian cells: 2.0

Non-coding RNAs—Novel targets in neurotoxicity

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