Inhibitor of Apoptosis Proteins Gene Expression and Its Correlation with Prognostic Factors in Primary and Metastatic Uveal Melanoma

Lederman, Michal; Meir, Tal; Zeschnigk, Michael; Pe’er, Jacob; Chowers, Itay

doi:10.1080/02713680802382989

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…BIRC5 and BIRC7 were among the top 5 DEG associated with inhibition of apoptosis and regulation of proteolysis. Both factors belong to the "inhibitors of apoptosis proteins" family and are upregulated in uveal melanoma as well 39 . The most significantly upregulated DEG in CM was LHFPL3, which is also highly expressed in malignant glioma and can be inhibited by miRNA-218-5p thus reducing the invasiveness of glioma cells 40 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures

Wolf¹,

Auw-Haedrich²,

Schlecht³

et al. 2020

Sci Rep

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This study characterizes the transcriptome and the cellular tumor microenvironment (TME) of conjunctival melanoma (CM) and identifies prognostically relevant biomarkers. 12 formalin-fixed and paraffin-embedded CM were analyzed by MACE RNA sequencing, including six cases each with good or poor clinical outcome, the latter being defined by local recurrence and/or systemic metastases. Eight healthy conjunctival specimens served as controls. The TME of CM, as determined by bioinformatic cell type enrichment analysis, was characterized by the enrichment of melanocytes, pericytes and especially various immune cell types, such as plasmacytoid dendritic cells, natural killer T cells, B cells and mast cells. Differentially expressed genes between CM and control were mainly involved in inhibition of apoptosis, proteolysis and response to growth factors. POU3F3, BIRC5 and 7 were among the top expressed genes associated with inhibition of apoptosis. 20 genes, among them CENPK, INHA, USP33, CASP3, SNORA73B, AAR2, SNRNP48 and GPN1, were identified as prognostically relevant factors reaching high classification accuracy (area under the curve: 1.0). The present study provides new insights into the TME and the transcriptional profile of CM and additionally identifies new prognostic biomarkers. These results add new diagnostic tools and may lead to new options of targeted therapy for CM.

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Section: Discussionmentioning

confidence: 99%

Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures

Wolf¹,

Auw-Haedrich²,

Schlecht³

et al. 2020

Sci Rep

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show abstract

“…We therefore determined the transcription level of a protein belonging to the Inhibitor of apoptosis family (IAP), the cell cycle and apoptosis regulatory 1 protein (CARP) and the cellular apoptosis susceptibility protein (CAS). IAP levels increase in certain tumors probably contributing to resistance to apoptosis [39], CAS and CARP are also both involved in apoptosis [22], [40], [41]: CARP is a novel cell growth regulator [42] and CAS is necessary in the mitotic spindle checkpoint that ensures genomic stability during cell division [41]. In addition, we also analyzed microtubule subunits (alpha and beta tubulins), necessary for mitotic spindle formation.…”

Section: Introductionmentioning

confidence: 99%

Molecular Evidence of the Toxic Effects of Diatom Diets on Gene Expression Patterns in Copepods

et al. 2011

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BackgroundDiatoms are dominant photosynthetic organisms in the world's oceans and are considered essential in the transfer of energy through marine food chains. However, these unicellular plants at times produce secondary metabolites such as polyunsaturated aldehydes and other products deriving from the oxidation of fatty acids that are collectively termed oxylipins. These cytotoxic compounds are responsible for growth inhibition and teratogenic activity, potentially sabotaging future generations of grazers by inducing poor recruitment in marine organisms such as crustacean copepods.Principal FindingsHere we show that two days of feeding on a strong oxylipin-producing diatom (Skeletonema marinoi) is sufficient to inhibit a series of genes involved in aldehyde detoxification, apoptosis, cytoskeleton structure and stress response in the copepod Calanus helgolandicus. Of the 18 transcripts analyzed by RT-qPCR at least 50% were strongly down-regulated (aldehyde dehydrogenase 9, 8 and 6, cellular apoptosis susceptibility and inhibitor of apoptosis IAP proteins, heat shock protein 40, alpha- and beta-tubulins) compared to animals fed on a weak oxylipin-producing diet (Chaetoceros socialis) which showed no changes in gene expression profiles.ConclusionsOur results provide molecular evidence of the toxic effects of strong oxylipin-producing diatoms on grazers, showing that primary defense systems that should be activated to protect copepods against toxic algae can be inhibited. On the other hand other classical detoxification genes (glutathione S-transferase, superoxide dismutase, catalase, cytochrome P450) were not affected possibly due to short exposure times. Given the importance of diatom blooms in nutrient-rich aquatic environments these results offer a plausible explanation for the inefficient use of a potentially valuable food resource, the spring diatom bloom, by some copepod species.

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“…IAPs form a family of caspase inhibitors that inhibit the downstream portion of the apoptosis pathway and inhibit cell death in response to multiple stimuli (28). There are currently eight known human IAP family members, with IAP3 being the best characterized member (29). The antiapoptotic roles of IAP3 have been attributed to its ability to directly bind to and inhibit the activated forms of caspase-3, -7 and -9, which are important executors of the intrinsic apoptosis pathway (30).…”

Section: Discussionmentioning

confidence: 99%

Matrine-induced apoptosis in Hep3B cells via the inhibition of MDM2

Zhou¹,

Li²,

Li³

et al. 2016

Molecular Medicine Reports

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Matrine, an alkaloid component derived from the Sophora root, can inhibit cancer cell proliferation and induce autophagy via p53 associated pathways. However, numerous tumor cells lack functional p53 and little is known about the effect of matrine on the p53‑deficient/mutant cancer cells. The present study aimed to assess anticancer effects of matrine in p53‑deficient human Hep3B hepatoma cells. The present results demonstrated that matrine caused Hep3B cell apoptosis by suppressing gene expression of minute double‑mutant (MDM)2. Notably, it was revealed that matrine inhibited MDM2 at the transcriptional level in a time‑ and dose‑dependent manner. This MDM2 inhibition resulted in induction of the p53 family member, p73; however, the functions of p73 were not induced since matrine‑induced p73 failed to activate its target genes, p21 and p53 upregulated modulator of apoptosis. The matrine‑induced downregulation of MDM2 led to an inhibition of inhibitor of apoptosis protein 3, which might serve a critical role in matrine‑induced apoptosis in MDM2‑overexpressing Hep3B cells. Finally, combination therapy of matrine with 100 µM epotoside successfully killed more Hep3B cells, suggesting that matrine can sensitize p53‑deficient Hep3B cells to epotoside‑induced apoptosis.

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Inhibitor of Apoptosis Proteins Gene Expression and Its Correlation with Prognostic Factors in Primary and Metastatic Uveal Melanoma

Cited by 7 publications

References 22 publications

Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures

Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures

Molecular Evidence of the Toxic Effects of Diatom Diets on Gene Expression Patterns in Copepods

Matrine-induced apoptosis in Hep3B cells via the inhibition of MDM2

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