Tristetraprolin Posttranscriptionally Downregulates TRAIL Death Receptors

Lee, Won Hyeok; Han, Myung Woul; Kim, Song Hee; Seong, Daseul; An, Jae Hee; Chang, Hyo Won; Kim, Sang Yoon; Kim, Seong Who; Lee, Mi Kyung

doi:10.3390/cells9081851

Cited by 5 publications

(5 citation statements)

References 33 publications

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“…In our results, the candidate differentially expressed eccDNAs were mainly derived from the 5'-, 3'-UTRs, and the CpG region, rather than exons, introns or repeat sequences. Previous studies demonstrated that the 5'-, 3'-UTR, and CpG region play important roles in the regulation of RNA translatability and stability, as well as RNA transcription (19)(20)(21). Hence, it is possible that miRNA or si-like RNA generated by the eccDNAs could transcriptionally or posttranscriptionally affect the levels of the corresponding RNA, especially those of oncogenes or tumor suppressor genes, and participate in ESCC induction and progression.…”

Section: Discussionmentioning

confidence: 99%

Extrachromosomal circular DNAs are common and functional in esophageal squamous cell carcinoma

Sun¹,

Ji²,

Zhao³

et al. 2021

Ann Transl Med

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Background: Esophageal squamous cell carcinoma (ESCC) is the leading cause of cancer-related mortality.While recent studies have documented the presence of extrachromosomal circular DNAs (eccDNAs) in various tumors, to date, there have been no studies examining the distribution and function of eccDNAs in ESCC.Methods: The eccDNAs from three surgically matched ESCC tissue samples were extracted and amplified by rolling circle amplification after removal of linear DNA and mitochondrial circular DNA. Highthroughput eccDNA sequencing and bioinformatics analysis was performed to study the distribution pattern and the level of eccDNA expression. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the genes associated with the differentially expressed eccDNAs. Five up-regulated and five down-regulated candidate eccDNAs were validated by routine polymerase chain reaction (PCR), TOPO-TA cloning and Sanger sequencing. The nucleotides flanking the eccDNA junctions were analyzed to explore the mechanisms of eccDNA formation.Results: A total of 184,557 eccDNAs was identified. The overall length distribution ranged from 33 to 96,8842 base pairs (bp), with the peak at approximately 360 bp. These eccDNAs mainly originated from 5'-and 3'-untranslated regions (UTRs), and rarely from exons, introns, LINE, or Alu repeat regions. The chromosome distribution, length distribution, and genomic annotation of the eccDNAs were comparable between ESCC samples and matched normal epithelium. Nevertheless, 16,031 eccDNAs were found to be differentially expressed between ESCC and matched normal epithelium, including 10,126 up-regulated eccDNAs and 5,905 down-regulated eccDNAs. GO analysis and KEGG pathway analysis showed enriched in cancer pathways, mitogen-activated protein kinase (MAPK) pathway, GTPase-related activity, and cytoskeleton function. PCR, TOPO-TA cloning, and Sanger sequencing validated the junctional sites of five up-regulated candidate eccDNAs and four other unexpected eccDNAs. A repeat nucleotide pattern between the position flanking the start site and that flanking the end site was detected.Conclusions: This study demonstrated the genome-wide presence of eccDNAs, explored the differential expression of eccDNAs, and revealed the potential mechanisms of eccDNAs in ESCC. This work provides further insights into our understanding of genome plasticity, the role of eccDNAs in ESCC, and may contribute to the development of potential clinical therapies.

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Section: Discussionmentioning

confidence: 99%

Extrachromosomal circular DNAs are common and functional in esophageal squamous cell carcinoma

Sun¹,

Ji²,

Zhao³

et al. 2021

Ann Transl Med

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“…TTP, the most common RNA-binding protein, has been shown to be involved in the regulation of various ARE-containing mRNAs ( Lee et al, 2020 ). The absence of TTP increased the expression and proliferation of its activation markers, and inhibited apoptosis in T cells ( Moore et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Tristetraprolin Gene Single-Nucleotide Polymorphisms and mRNA Level in Patients With Rheumatoid Arthritis

et al. 2021

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To observe and evaluate the correlation between single-nucleotide polymorphisms (SNPs) and messenger RNA (mRNA) level related to tristetraprolin (TTP) in Chinese rheumatoid arthritis (RA). TapMan SNP was used for genotyping analysis in 580 RA patients and 554 healthy people. Association between TTP gene polymorphisms (rs251864 and rs3746083) and RA was obtained. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) technology was applied for the detection of TTP mRNA level in peripheral blood mononuclear cells (PBMCs) in 36 RA patients and 37 healthy people. We observed that the allele T of TTP rs3746083 increased RA susceptibility (p = 0.019). A significant difference was found under the dominant model of rs3746083 (p = 0.037). Further analysis showed the allele distribution of rs3746083 was nominally correlated with RF phenotype of RA patients (p = 0.045). Nevertheless, the association between TTP rs251864 and the incidence of RA was no statistically significant (p > 0.05). The TTP expression level in PBMCs of RA patients was significantly reduced (p < 0.001). In conclusion, the results of this experiment support that TTP may be involved in the pathogenesis of RA.

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“…Tristetraprolin physically associated with AREs in DR4 and DR5 and enhanced the decay of DR4/5 mRNAs. Tristetraprolin overexpression in colon cancer cells enhanced TRAIL resistance but downregulation of tristetraprolin increased TRAIL sensitivity via DR4/5 expression (8).…”

Section: Recent Breakthroughs In Trail-driven Signaling: Fresh From T...mentioning

confidence: 94%

“…Tristetraprolin, an ARE-binding protein has a critical role in the modulation of mRNA stability of death receptors (8). DR4 mRNA contained three AREs and DR5 mRNA contained four AREs in 3'-UTR.…”

Section: Recent Breakthroughs In Trail-driven Signaling: Fresh From T...mentioning

confidence: 99%

TRAIL mediated signaling in different cancers: cancer in the "Crosshairs"

Farooqi

Naureen

Yılmaz

et al. 2020

Cell Mol Biol (Noisy-le-grand)

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Cancer is a therapeutically challenging disease because of its heterogeneous and multifaceted nature. Decades of research have sequentially and systematically enabled us to develop a sharper and better understanding of the heterogeneous nature of cancer. Genetic, genomic and proteomic studies have unraveled wide-ranging signaling cascades which play cornerstone role in disease onset and progression. More importantly, activation of pro-survival signaling and loss of apoptosis also play critical role in cancer progression. TRAIL-mediated signaling pathway has emerged as one of the most comprehensively analyzed cascade because of its exceptional ability to target cancer cells while leaving normal cells intact. TRAIL discovery and landmark achievements related to TRAIL/TRAIL-receptor signaling pathway attracted the attention of researchers. Therefore, scientists started to add missing pieces to an incomplete jig-saw puzzle and allowed contemporary researchers to conceptualize a better molecular snapshot of TRAIL-induced signaling in various cancers. Circumstantial evidence illuminated a functionally unique "push and pull" between anti-apoptotic and pro-apoptotic proteins in different cancers. Overexpression of anti-apoptotic proteins and inactivation of pro-apoptotic proteins shifted the balance towards loss of apoptosis. There has been a breakneck increase in the number of clinical trials related to TRAIL-based therapeutics which validate the true pharmacological potential of TRAIL-based therapeutics as effective anticancer agents. However, apart from advancements in our clinical understanding about the efficacy of TRAIL-based therapeutics, researchers have also faced setbacks in the field of translational medicine. Therefore, in this review, we have attempted to set spotlight on the most recent and landmark discoveries which have leveraged our understanding related to TRAIL-mediated signaling altogether to a new level.

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Tristetraprolin Posttranscriptionally Downregulates TRAIL Death Receptors

Cited by 5 publications

References 33 publications

Extrachromosomal circular DNAs are common and functional in esophageal squamous cell carcinoma

Extrachromosomal circular DNAs are common and functional in esophageal squamous cell carcinoma

Tristetraprolin Gene Single-Nucleotide Polymorphisms and mRNA Level in Patients With Rheumatoid Arthritis

TRAIL mediated signaling in different cancers: cancer in the "Crosshairs"

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