Post-Transcriptional Fine-tuning of COP9 Signalosome Subunit Biosynthesis is Regulated by the c-Myc/Lin28B/let-7 Pathway

Leppert, Ulrike; Henke, Wolfgang; Huang, Xiaohua; Müller, J. M.; Dubiel, Wolfgang

doi:10.1016/j.jmb.2011.04.041

Cited by 37 publications

(34 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Leppert et al recently observed that mRNA levels of COP9 genes were regulated by let-7 miRNA [20]. To probe the importance of the regulatory mechanism by miRNA, the TCGA miRNA dataset was used to determine the gene expression correlation of COP9 genes and the let-7 miRNA species (Additional file 2: Table S1).…”

Section: Resultsmentioning

confidence: 99%

“…Down-regulation of COPS5 in mouse embryonic fibroblasts drastically decreased the stability of COPS1, COPS3, and COPS8 [17–19]. Therefore, it is plausible that coordinated expression of COP9 genes is needed to maintain necessary amounts of COP9 and imbalance may be associated with disease [20]. To elucidate this possibility, a statistically adequate number of normal tissues must be analyzed with precision for their gene expressions.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of RNA expression of normal and cancer tissues reveals high correlation of COP9 gene expression with respiratory chain complex components

Wicker

Izumi

2016

BMC Genomics

View full text Add to dashboard Cite

BackgroundThe COP9 signalosome, composed of eight subunits, is implicated in cancer genetics with its deneddylase activity to modulate cellular concentration of oncogenic proteins such as IkB and TGFβ. However, its function in the normal cell physiology remains elusive. Primarily focusing on gene expression data of the normal tissues of the head and neck, the cancer genome atlas (TCGA) database was used to identify groups of genes that were expressed synergistically with the COP9 genes, particularly with the COPS5 (CSN5), which possesses the catalytic activity of COP9.ResultsExpressions of seven of the COP9 genes (COPS2, COPS3, COPS4, COPS5, COPS6, COPS7A, and COPS8) were found to be highly synergistic in the normal tissues. In contrast, the tumor tissues decreased the coordinated expression pattern of COP9 genes. Pathway analysis revealed a high coordination of the expression of the COPS5 and the other COP9 genes with mitochondria-related functional pathways, including genes encoding the respiratory chain complex.ConclusionsThe results indicate that mRNA expression data for the matched normal tissues available in TCGA are statistically reliable, and are highly useful to assess novel associations of genes with functional pathways in normal physiology as well as in the cancer tissues. This study revealed the significant correlation between the expressions of the COP9 genes and those related to the mitochondrial activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3313-y) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analysis of RNA expression of normal and cancer tissues reveals high correlation of COP9 gene expression with respiratory chain complex components

Wicker

Izumi

2016

BMC Genomics

View full text Add to dashboard Cite

show abstract

“…1a,b) 20 . Both IFNs and nuclear factor-kB cascades activate the STAT3/Myc/ Lin28B axis, repressing expression of miRNAs from the let-7 family 18,[21][22][23] . Indeed, in HeLa cells, 24-h IFNa treatment inhibited let-7i and let-7g expression by 80 and 60%, respectively, while miR-21 was unaffected (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, multiple proteins involved in IFN signalling or downstream IFN-stimulated proteins are sumoylated 16,17 . Among IFN/STAT1/3 targets is the RNA binding protein Lin28B, a key developmental regulator implicated in stemness, cancer growth and metabolism 18,19 . Lin28 is one of the essential human genes contributing to iPSC reprogramming, and Lin28 expression is enriched in various somatic progenitors, as well as in germline and embryonic stem cells 19 .…”

mentioning

confidence: 99%

Interferon controls SUMO availability via the Lin28 and let-7 axis to impede virus replication

Şahin¹,

Ferhi²,

Carnec³

et al. 2014

Nat Commun

View full text Add to dashboard Cite

Small ubiquitin-related modifier (SUMO) protein conjugation onto target proteins regulates multiple cellular functions, including defence against pathogens, stemness and senescence. SUMO1 peptides are limiting in quantity and are thus mainly conjugated to high-affinity targets. Conjugation of SUMO2/3 paralogues is primarily stress inducible and may initiate target degradation. Here we demonstrate that the expression of SUMO1/2/3 is dramatically enhanced by interferons through an miRNA-based mechanism involving the Lin28/let-7 axis, a master regulator of stemness. Normal haematopoietic progenitors indeed display much higher SUMO contents than their differentiated progeny. Critically, SUMOs contribute to the antiviral effects of interferons against HSV1 or HIV. Promyelocytic leukemia (PML) nuclear bodies are interferon-induced domains, which facilitate sumoylation of a subset of targets. Our findings thus identify an integrated interferon-responsive PML/SUMO pathway that impedes viral replication by enhancing SUMO conjugation and possibly also modifying the repertoire of targets. Interferon-enhanced post-translational modifications may be essential for senescence or stem cell self-renewal, and initiate SUMO-dependent proteolysis.

show abstract

“…The hsa-let-7 family targets PRDM1 and regulates its function in a diffuse large B-cell lymphoma 73 . Hsa-miR-217 targets E2F3 which is positively associated with the hepatocellular carcinoma metastasis 74 .…”

Section: Resultsmentioning

confidence: 99%

Identifying the miRNA signature associated with survival time in patients with lung adenocarcinoma using miRNA expression profiles

Sathipati

2017

Sci Rep

View full text Add to dashboard Cite

Lung adenocarcinoma is a multifactorial disease. MicroRNA (miRNA) expression profiles are extensively used for discovering potential theranostic biomarkers of lung cancer. This work proposes an optimized support vector regression (SVR) method called SVR-LUAD to simultaneously identify a set of miRNAs referred to the miRNA signature for estimating the survival time of lung adenocarcinoma patients using their miRNA expression profiles. SVR-LUAD uses an inheritable bi-objective combinatorial genetic algorithm to identify a small set of informative miRNAs cooperating with SVR by maximizing estimation accuracy. SVR-LUAD identified 18 out of 332 miRNAs using 10-fold cross-validation and achieved a correlation coefficient of 0.88 ± 0.01 and mean absolute error of 0.56 ± 0.03 year between real and estimated survival time. SVR-LUAD performs well compared to some well-recognized regression methods. The miRNA signature consists of the 18 miRNAs which strongly correlates with lung adenocarcinoma: hsa-let-7f-1, hsa-miR-16-1, hsa-miR-152, hsa-miR-217, hsa-miR-18a, hsa-miR-193b, hsa-miR-3136, hsa-let-7g, hsa-miR-155, hsa-miR-3199-1, hsa-miR-219-2, hsa-miR-1254, hsa-miR-1291, hsa-miR-192, hsa-miR-3653, hsa-miR-3934, hsa-miR-342, and hsa-miR-141. Gene ontology annotation and pathway analysis of the miRNA signature revealed its biological significance in cancer and cellular pathways. This miRNA signature could aid in the development of novel therapeutic approaches to the treatment of lung adenocarcinoma.

show abstract

Post-Transcriptional Fine-tuning of COP9 Signalosome Subunit Biosynthesis is Regulated by the c-Myc/Lin28B/let-7 Pathway

Cited by 37 publications

References 51 publications

Analysis of RNA expression of normal and cancer tissues reveals high correlation of COP9 gene expression with respiratory chain complex components

Analysis of RNA expression of normal and cancer tissues reveals high correlation of COP9 gene expression with respiratory chain complex components

Interferon controls SUMO availability via the Lin28 and let-7 axis to impede virus replication

Identifying the miRNA signature associated with survival time in patients with lung adenocarcinoma using miRNA expression profiles

Contact Info

Product

Resources

About