Complexity of <i>COX</i>-<i>2</i> gene regulation

Harper, Kelly; Tyson-Capper, Alison

doi:10.1042/bst0360543

Cited by 97 publications

(86 citation statements)

References 17 publications

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“…miR-101b and miR-26b are differentially expressed in LPS-treated macrophages from young and aged mice In many cases, the altered miRNA level could reflect COX-2 expression at the post-transcriptional level (Harper and Tyson-Capper 2008). Previously, we have profiled the expression of miRNAs in LPS-treated and untreated macrophages from young and aged mice using the microarray technology and showed that miR101b and miR-26b were differentially expressed in the two age groups (Jiang et al 2012) (Fig.…”

Section: Lps Enhances Expression Of Cox-2 and Pge2 In Aged Mouse Perimentioning

confidence: 98%

Dysregulated expression of miR-101b and miR-26b lead to age-associated increase in LPS-induced COX-2 expression in murine macrophage

Liú

Wang

et al. 2015

AGE

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Aging is the natural process of decline in physiological structure and function of various molecules, cells, tissues, and organs. Growing evidence indicates that increased immune genetic diversity and dysfunction of immune system cause aging-related pathophysiological process with the growth of age. In the present study, we observed that LPS-induced higher activation of cyclooxygenase (COX)-2 promoter is associated with the upregulated binding activity of nuclear factor kappa B (NF-κB) in peritoneal macrophages of aged mice than young ones. Additionally, COX-2 is a direct target of miR-101b and miR-26b in the macrophages. Significant upregulation of miR-101b and miR26b effectively prevented LPS-induced excessive expression of COX-2 in the young mice. Because these negative regulatory factors were unresponsive to LPS stimulation, the levels of COX-2 were markedly higher in the macrophages of aged mice. Further study showed that NF-κB activation contributed to the increase in the expression of miR-101b and miR-26b in the LPSstimulated macrophages of young mice, but not aged ones. Moreover, histone deacetylase (HDAC) inhibitor trichostatin A (TSA) upregulated expression of miR101b and miR-26b in the aged mouse macrophages only, but not the young cells. This demonstrated that HDAC suppressed the expression of miR-101b and miR-26b in the LPS-treated macrophages of aged mice and contributed to the aging process. TSA-induced increased expression of miR-101b and miR-26b could further suppress COX-2 expression. These findings provide novel evidence on the regulation of immune senescence and miR-101b and miR-26b, which might be promising targets in treating aged-related inflammatory diseases. Epigenetic regulation of the microRNAs (miRNAs) provides an important evidence for the treatment of innate inflammatory disease with HDAC inhibitors in elderly.

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Section: Lps Enhances Expression Of Cox-2 and Pge2 In Aged Mouse Perimentioning

confidence: 98%

Dysregulated expression of miR-101b and miR-26b lead to age-associated increase in LPS-induced COX-2 expression in murine macrophage

Liú

Wang

et al. 2015

AGE

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“…In addition, COX-1 is highly expressed in gastric epithelial cells where it plays an important role in cytoprotection through the generation of prostanoids, such as prostaglandin E2 (PGE2) [31,33] . In contrast, COX-2 gene, a primary response one with many regulatory sites [34] , is constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer [35] . In cancer cells, the major prostanoid produced through COX-2 is PGE2, which plays important roles in modulating motility, proliferation and resistance to apoptosis [36,37] .…”

Section: Mechanism Of Action Of Aspirinmentioning

confidence: 99%

Aspirin, cyclooxygenase inhibition and colorectal cancer

Sostres

Gargallo

Lanas

2014

WJGPT

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Colorectal cancer (CRC) is the third most common type of cancer worldwide. Screening measures are far from adequate and not widely available in resourcepoor settings. Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC. Increasing evidence from epidemiological studies, randomized clinical trials and basic science supports the effectiveness of aspirin, as well as other non-steroidal anti-inflammatory drugs, for chemoprevention of several types of cancer, including CRC. This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality. The detectable benefit of daily low-dose aspirin (at least 75 mg), as used to prevent cardiovascular disease events, strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy. Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (about 20 minutes); nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Aspirin; Colorectal cancer; Cyclooxygenase inhibition; Mechanisms; Risk; Benefits Core tip: Colorectal cancer (CRC) is a major cause of morbidity and mortality worldwide. Currently, CRC screening programs are not widely available and need to be improved. New prevention strategies are therefore necessary. Daily low-dose aspirin, as given for the prevention of cardiovascular disease events, has demonstrated benefits in clinical and basic studies in terms of preventing adenoma recurrence and decreasing the incidence of CRC and attributable mortality. These findings indicate that the antiplatelet action of aspirin plays a central role in its antitumor effect. Cyclooxygenasedependent and independent mechanisms have been suggested to explain this effect. Extensive translational medical research is mandatory for future progress in CRC prevention.Sostres C, Gargallo CJ, Lanas A. Aspirin, cyclooxygenase inhibition and colorectal cancer.

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“…The expression of the prostaglandin synthetase-2 gene (PTGS-2 ⁄ COX-2) is regulated at both transcriptional and post-transcriptional levels (9), and several studies have reported the role of )765G>C and )1195A>G polymorphisms in the promoter region as risk factors for various cancers (10). We have previously reported the possible association of polymorphisms )765G>C and )1195A>G with subgroups of patients with NMSC after transplantation (11).…”

Section: Introductionmentioning

confidence: 99%

“…It has 22 repeats of adenylate and uridylate-rich (AU-rich ⁄ AREs) elements, whose binding trans-acting factors influence the stabilization and ⁄ or mRNA processing and nucleocytoplasmic transport (9). Furthermore, 3¢UTR has many putative binding sites for several microRNAs (http:// www.targetscan.org) that might affect the stability and translation of mRNAs (9,14). Sequence variation affecting trans-acting factors or microRNA binding sites may interfere with mRNA stability and translation by altering polyadenylation, protein::mRNA and miRNA::mRNA regulatory interactions, contributing towards differential PTGS-2 expression and a substantial degree of interindividual variability in susceptibility to cancer.…”

Section: Introductionmentioning

confidence: 99%

“…The proximal polyadenylation signal has a non-consensus cleavage polyadenylation specificity factor binding site (AUUAAA) followed by putative upstream enhancer elements (USEs) (9). It has 22 repeats of adenylate and uridylate-rich (AU-rich ⁄ AREs) elements, whose binding trans-acting factors influence the stabilization and ⁄ or mRNA processing and nucleocytoplasmic transport (9). Furthermore, 3¢UTR has many putative binding sites for several microRNAs (http:// www.targetscan.org) that might affect the stability and translation of mRNAs (9,14).…”

Section: Introductionmentioning

confidence: 99%

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Analysis of the 3′UTR of the prostaglandin synthetase-2 (PTGS-2 / COX-2) gene in non-melanoma skin cancer after organ transplantation

Gomez-Lira¹,

Tessari²,

Mazzola³

et al. 2011

Experimental Dermatology

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To define the potential involvement of polymorphisms in the 3¢untranslated region (3¢UTR) of the prostaglandin synthetase-2 (PTGS-2) gene to non-melanoma skin cancer (NMSC) predisposition after transplantation, we screened for genetic variant, relevant parts of this region. It contains binding sites for trans-acting factors, an alternative polyadenylation site and putative target sequences for miRNAs. Variant +8473T>C did not appear to play a functional role in the regulation of gene expression in human keratinocyte-transfected cells. In addition to the well-known +8473T>C, we identified four polymorphisms: +8293G>C, +10259T>G, +10267G>A and +10335G>A. No allele frequency differences were observed between cases and controls neither for +8473T>C nor for any of the identified polymorphisms, suggesting that polymorphisms in the 3¢UTR of the PTGS2 gene are rare and unlikely to represent risk factor for NMSC after transplantation.

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Complexity of COX-2 gene regulation

Cited by 97 publications

References 17 publications

Dysregulated expression of miR-101b and miR-26b lead to age-associated increase in LPS-induced COX-2 expression in murine macrophage

Dysregulated expression of miR-101b and miR-26b lead to age-associated increase in LPS-induced COX-2 expression in murine macrophage

Aspirin, cyclooxygenase inhibition and colorectal cancer

Analysis of the 3′UTR of the prostaglandin synthetase-2 (PTGS-2 / COX-2) gene in non-melanoma skin cancer after organ transplantation

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