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At least 235 records · Page 13Linked to original sources
PubMed1996

Interleukin-11 mRNA stabilization in phorbol ester-stimulated primate bone marrow stromal cells.

12-O-Tetradecanoylphorbol-13-acetate (TPA) stimulation of PU-34 cells, a primate bone marrow stromal cell line, resulted in a prolonged elevation of interleukin-11 (IL-11) mRNA, which can be inhibited by protein synthesis inhibitors. Nuclear run-on assays and actinomycin D experiments demonstrated that the up-regulation of IL-11 gene expression is mainly controlled at the posttranscriptional level through the protein kinase C (PKC) pathway. Inhibition of PKC activity by calphostin C generated an IL-11 mRNA degradation intermediate in TPA-stimulated PU-34 cells. This intermediate retains the 5' untranslated region (5'UTR) and coding region of the IL-11 mRNA but has lost the poly(A) tail and the 3'UTR. The mechanisms underlying IL-11 mRNA stabilization were further investigated by transfections with a variety of chimeric IL-11 constructs and deletion mutants. Two important observations were made from these transient expression experiments: (i) the same 3'UTR of IL-11 mRNA shown to confer instability in one chimeric transcript may not function as a destabilizer in another chimeric RNA, and (ii) the 5'UTR, coding region, and 3'UTR all contribute to IL-11 mRNA decay, and labile IL-11 deletion transcripts are not necessarily stabilized by TPA stimulation. Our study suggests that multiple regions within the IL-11 mRNA are involved in TPA-stimulated IL-11 mRNA stabilization, possibly through a unique RNA folding conformation involving interactions of various RNA sequences within the IL-11 mRNA molecule.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Overexpression of the class II P-glycoprotein gene in primary rat hepatocyte culture: evidence for increased mRNA stability.

The overexpression of P-glycoprotein (Pgp) appears to be responsible for multidrug resistance in some human cancers. The molecular basis of this overexpression is not understood. We have used primary monolayer cultures of adult rat hepatocytes as a model system to study the regulation of Pgp gene expression (Lee et al., J. Cell. Physiol., 157: 392-402, 1993). We observed a dramatic and specific overexpression of class II Pgp as a function of the time in culture. This isoform of Pgp, which is expressed at a very low level in normal liver, has also been shown to be predominantly overexpressed in several models of rat liver carcinogenesis. In the present study, we have used nuclear run-on assays and mRNA decay studies to investigate the mechanism for the overexpression of class II Pgp in cultured hepatocytes. We conclude that an increased mRNA stability is the major factor involved in the increased expression of class II Pgp. Studies using various drugs indicate that the integrity of the cytoskeleton is important for the maintenance of high expression of class II Pgp. Disruption of the cytoskeleton in cultured hepatocytes with cytochalasin D did not affect the transcriptional activity of the class II Pgp gene but rapidly destabilized its mRNA. This raises the possibility that an association between class II Pgp mRNA and cytoskeletal elements may underlie the mechanism that regulates class II Pgp mRNA stability. These findings have important implications for our understanding of the overexpression of class II Pgp during liver carcinogenesis.

Actins↗
PubMed2004

IL-17A augments TNF-alpha-induced IL-6 expression in airway smooth muscle by enhancing mRNA stability.

BACKGROUND: IL-17A is implicated in the regulation of inflammation and is found in increased amounts in the asthmatic airway. Human airway smooth muscle (ASM) cells synthesize cell adhesion molecules and cytokines in response to inflammatory mediators. OBJECTIVE: In this study, we examined whether IL-17A modulated the synthetic function of ASM cells. METHODS: Primary ASM cultures were treated with IL-17A alone and in combination with the proinflammatory cytokines TNF-alpha and IL-1beta. Intercellular adhesion molecule 1 expression, GM-CSF, and IL-6 secretion were measured by ELISA. Examination of transcriptional regulation was performed via transient transfection of promoter constructs, whereas mRNA stability was assessed by actinomycin D chase and quantitative real-time PCR. RESULTS: Airway smooth muscle did not secrete IL-17A after stimulation of ASM with TNF-alpha and IL-1beta. Furthermore, IL-17A (0.1-10 ng/mL) had no effect on TNF-alpha-induced and IL-1beta-induced intercellular adhesion molecule 1 expression or GM-CSF secretion. However, IL-17A (10 ng/mL) significantly augmented TNF-alpha-induced IL-6 secretion 12-fold (TNF-alpha, 2.3 +/- 0.4 ng/mL; IL-17A and TNF-alpha, 27.5 +/- 4.8 ng/mL; P <.05) while having no effect on IL-1beta-induced IL-6. Although IL-17A had no effect on nuclear factor kappaB-mediated transcriptional regulation of IL-6 gene expression induced by TNF-alpha, IL-17A significantly augmented TNF-alpha-induced IL-6 mRNA stability. CONCLUSION: Collectively, these results demonstrate that IL-17A amplifies the synthetic function of ASM cells, acting via a posttranscriptional pathway, rather than transcriptional mechanisms, to augment TNF-alpha-induced secretion of IL-6 from ASM cells.

Bronchi↗
PubMed2003

Chemically modified tetracyclines selectively inhibit IL-6 expression in osteoblasts by decreasing mRNA stability.

In bone biology, interleukin (IL)-6 is an autocrine/paracrine cytokine which can induce osteoclasts formation and activation to help mediate inflammatory bone destruction. Previous studies have shown that tetracycline and its derivatives have potentially beneficial therapeutic effects in the prevention and treatment of metabolic bone diseases by modulating osteoblast and osteoclast activities. Our previous studies indicated that non-antimicrobial chemically modified tetracyclines (CMTs) can dose-dependently inhibit IL-1 beta-induced IL-6 secretion in osteoblastic cells. In the present study, we explored the molecular mechanisms underlying the ability of doxycycline analogs CMT-8 and its non-chelating pyrazole derivative, CMT-5 to affect IL-6 gene expression in murine osteoblasts. Steady-state IL-6 mRNA was decreased with CMT-8 (ca. 50%) but not by CMT-5 when stimulated by IL-1 beta. CMT-8 regulation of IL-1 beta-induced IL-6 gene expression was further explored. CMT-8 did not affect IL-6 promoter activity in reporter gene assays. However, the IL-6 mRNA stability was decreased in the presence of CMT-8. These effects require de novo protein synthesis as they were inhibited by cycloheximide. Western blot analysis indicated that CMT-8 did not affect p38 mitogen-activated protein kinase, c-jun NH(2)-terminal kinases, or extracellular signal-regulated kinases (1 and 2) phosphorylation in response to IL-1 beta. These data suggest that CMT-8 can modulate inhibit IL-1 beta-induced IL-6 expression in MC3T3-E1 cells at the post-transcriptional level affecting IL-6 mRNA stability. These observations may offer a novel molecular basis for this treatment of metabolic bone diseases that are mediated by IL-6.

Animals↗
PubMed1999

CHOP/GADD153 and methionyl-tRNA synthetase (MetRS) genes overlap in a conserved region that controls mRNA stability.

The transcription factor CHOP is involved in the regulation of the cell division cycle and the control of programmed cell death in response to cellular stress. CHOP expression has been linked with several forms of cancer. A reciprocal translocation between the CHOP and TLS RNA-binding protein gene results in myxoid liposarcoma and amplifications of the CHOP gene are associated with solid tumors including several types of sarcomas. Here we report the mapping of the methionyl tRNA synthetase (MetRS) gene to the identical 12q13 locus where the CHOP gene had previously been mapped. PCR analysis demonstrates a tail-to-tail overlap of both genes over a 55-bp region. As a result the two mRNAs share a 3' UTR complementary sequence allowing an in vivo interaction between the two mRNAs. An AU-rich regulatory element (ARE) known to control mRNA stability resides in the overlapping sequence. To test for functional significance of the ARE a luciferase reporter plasmid containing the 3'UTR of CHOP was constructed. Transfection experiments in NIH-3T3 cells show that CHOP 3'UTR confers a significantly lower activity than a control reporter or a reporter in which the region overlapping the MetRS mRNA is deleted. The conservation of this overlapping of the CHOP and MetRS genes and the role of their complementary sequence in the control of mRNA stability suggest the existence of a functional link between the expression of these two genes.

3' Untranslated Regions↗
PubMed2001

Control of insulin mRNA stability in rat pancreatic islets. Regulatory role of a 3'-untranslated region pyrimidine-rich sequence.

Stabilization of insulin mRNA in response to glucose is a significant component of insulin production, but the mechanisms governing this process are unknown. We presently observe that insulin mRNA is a highly abundant messenger and that the content of this mRNA is mainly controlled by changes in messenger stability. We also demonstrate specific binding of the polypyrimidine tract-binding protein to a pyrimidine-rich sequence located in the 3'-untranslated region (3'-UTR) of insulin mRNA. This binding was increased in vitro by dithiothreitol and in vivo by glucose. Inhibition of polypyrimidine tract-binding protein binding to the pyrimidine-rich sequence by mutation of the core binding site resulted in a destabilization of a reporter gene mRNA. Thus, glucose-induced binding of polypyrimidine tract-binding protein to the 3'-UTR of insulin mRNA could be a necessary event in the control of insulin mRNA levels.

3' Untranslated Regions↗
PubMed2005

Platelet-derived growth factor stimulates Src-dependent mRNA stabilization of specific early genes in fibroblasts.

The Src family of protein-tyrosine kinases (SFKs) participates in a variety of signal transduction pathways, including promotion of cell growth, prevention of apoptosis, and regulation of cell interactions and motility. In particular, SFKs are required for the mitogenic response to platelet-derived growth factor (PDGF). However, it is not clear whether there is a discrete SFK-specific pathway leading to enhanced gene expression or whether SFKs act to generally enhance PDGF-stimulated gene expression. To examine this, we treated quiescent NIH3T3 cells with PDGF in the presence or absence of small molecule inhibitors of SFKs, phosphatidylinositol 3-kinase (PI3K), and MEK1/2. Global patterns of gene expression were analyzed by using Affymetrix Gene-Chip arrays, and data were validated by using reverse transcription-PCR and ribonuclease protection assay. We identified a discrete set of immediate early genes induced by PDGF and inhibited in the presence of the SFK-selective inhibitor SU6656. A subset of these SFK-dependent genes was induced by PDGF even in the presence of the MEK1/2 inhibitor U0126 or the PI3K inhibitor LY294002. By using ribonuclease protection assays and nuclear run-off assays, we further determined that PDGF did not stimulate the rate of transcription of these SFK-dependent immediate early genes but rather promoted mRNA stabilization. Our data suggest that PDGF regulates gene expression through an SFK-specific pathway that is distinct from the Ras-MAPK and PI3K pathways, and that SFKs signal gene expression by enhancing mRNA stability.

Animals↗
PubMed2001

Cross talk between beta(1) and alpha(V) integrins: beta(1) affects beta(3) mRNA stability.

There is increasing evidence that a fine-tuned integrin cross talk can generate a high degree of specificity in cell adhesion, suggesting that spatially and temporally coordinated expression and activation of integrins are more important for regulated cell adhesive functions than the intrinsic specificity of individual receptors. However, little is known concerning the molecular mechanisms of integrin cross talk. With the use of beta(1)-null GD25 cells ectopically expressing the beta(1)A integrin subunit, we provide evidence for the existence of a cross talk between beta(1) and alpha(V) integrins that affects the ratio of alpha(V)beta(3) and alpha(V)beta(5) integrin cell surface levels. In particular, we demonstrate that a down-regulation of alpha(V)beta(3) and an up-regulation of alpha(V)beta(5) occur as a consequence of beta(1)A expression. Moreover, with the use of GD25 cells expressing the integrin isoforms beta(1)B and beta(1)D, as well as two beta(1) cytoplasmic domain deletion mutants lacking either the entire cytoplasmic domain (beta(1)TR) or only its "variable" region (beta(1)COM), we show that the effects of beta(1) over alpha(V) integrins take place irrespective of the type of beta(1) isoform, but require the presence of the "common" region of the beta(1) cytoplasmic domain. In an attempt to establish the regulatory mechanism(s) whereby beta(1) integrins exert their trans-acting functions, we have found that the down-regulation of alpha(V)beta(3) is due to a decreased beta(3) subunit mRNA stability, whereas the up-regulation of alpha(V)beta(5) is mainly due to translational or posttranslational events. These findings provide the first evidence for an integrin cross talk based on the regulation of mRNA stability.

Animals↗
PubMed2006

Engagement of CD28 outside of the immunological synapse results in up-regulation of IL-2 mRNA stability but not IL-2 transcription.

During T cell activation by APC, CD28 is colocalized with TCR in the central supramolecular activation cluster (cSMAC) region of the immunological synapse. CD28 signaling through PI3K results in the recruitment of protein kinase C (PKC)theta to the cSMAC, activation of NF-kappaB, and induction of IL-2 transcription. These results suggest that localized engagement of CD28 within the cSMAC may be required for CD28 activation and/or signal integration with TCR signals. To test this model we have examined the mechanism of CD28-mediated induction of IL-2 secretion when CD28 is engaged outside of the immunological synapse. CD4 T cells were stimulated with Ag presented by B7-negative APC and CD28 costimulation was provided in trans by anti-CD28-coated beads or by class II-negative, B7-positive cells. We show that induction of IL-2 secretion under these conditions did not require expression of PKCtheta and did not induce NF-kappaB activation or IL-2 transcription. In contrast, CD28 costimulation in trans did induce IL-2 mRNA stability, accounting for the up-regulation of IL-2 secretion. These data indicate that the ability of CD28 to up-regulate IL-2 transcription requires colocalization of TCR and CD28 at the plasma membrane, possibly within the cSMAC of the immunological synapse. In contrast, the ability of CD28 to promote IL-2 mRNA stability can be transduced from a distal site from the TCR, suggesting that signal integration occurs downstream from the plasma membrane. These data support the potential role of trans costimulation in tumor and allograft rejection, but limit the potential functional impact that trans costimulation may have on T cell activation.

Active Transport, Cell Nucleus↗
PubMed2004

Cyclin mRNA stability does not vary during the cell cycle.

The cyclins are tightly regulated elements governing eukaryotic cell cycle progression by means of sequential activation-inactivation of cyclin-dependent kinases. In one manifestation of this regulation, the mRNA levels of several cyclin genes oscillate during the cycle in mammalian cells. Such cycle-dependent fluctuations in transcript levels could result from changes not only in rates of transcription, but also in mRNA stability. Here we used a new, minimally-disturbing method for producing multi-cycle synchronous growth of human MOLT-4 cells, in combination with quantitative real-time RT-PCR, to compare cell cycle-dependent transcript levels and half-lives of cyclin A2, B1, D3, E and PCNA mRNAs. While all mRNA levels except cyclin D3 varied in the cycle, there were no apparent variations in message half-lives. This differs from several previous reports of dramatic fluctuations in the stabilities of cyclin mRNAs, and infers that fluctuations in cyclin mRNA transcript levels during the MOLT-4 cell cycle are not due to variations in half-lives. The discrepancy in mRNA stability determinations could be due to differences in cell types or synchronization methods, but our findings may be representative of mRNA processing in the cycle of cells in unstressed steady-state growth.

Cell Cycle↗
PubMed2001

Superinduction of TNF-alpha and IL-6 in macrophages by vomitoxin (deoxynivalenol) modulated by mRNA stabilization.

Vomitoxin (VT or deoxynivalenol), a trichothecene, superinduces proinflammatory cytokine gene expression in vitro and in vivo. To better understand the underlying molecular mechanisms for this observation, post-transcriptional effects of VT on TNF-alpha and IL-6 gene expression were studied in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. VT was found to enhance both TNF-alpha and IL-6 protein secretion in the presence of LPS. Upon addition of the transcriptional inhibitor, 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB), secretion of both cytokines was inhibited. Using Northern analysis, the mRNA stabilities of TNF-alpha and IL-6 were studied in DRB-treated cells exposed to VT and LPS in both asynchronous and delayed synchronous modes. In the asynchronous model, cells were first incubated with LPS for 2 h, and then the medium was removed and replaced with medium containing DRB and VT. In the delayed synchronous model, cells were pretreated with LPS for 2 h and then DRB and VT were added to the culture. TNF-alpha and IL-6 mRNA were rapidly stabilized by VT (100 and 250 ng/ml) in both asynchronous and delayed synchronous models. In the asynchronous model, TNF-alpha mRNA half-life was 25 min but this was extended in the presence of 100 and 250 ng/ml of VT to >3 h. VT also extended half-lives of IL-6 mRNA from 60 min to >3 h. In the delayed synchronous model, the half-lives for TNF-alpha and IL-6 mRNA of 1.3 and 1.5 h, respectively, were extended to >3 h upon incubation with 100 and 250 ng/ml VT. These results suggest that post-transcriptional control via enhancement of mRNA stability is likely to contribute to proinflammatory cytokine superinduction in macrophages by VT and other trichothecenes.

Analysis of Variance↗
PubMed2005

Induction of TSP1 gene expression by heat shock is mediated via an increase in mRNA stability.

Thrombospondin-1 (TSP1) expression has previously been shown to be regulated primarily at the level of transcription. In the present study, transcriptional control was not involved in the induction of TSP1 by heat shock. In contrast, heat shock caused significant stabilization of TSP1 mRNA. Fusion of the 3'-untranslated region (UTR) of TSP1 mRNA, with a reporter gene, increased the stability of the reporter transcript by heat shock. Furthermore, we identified a putative region from 968 to 1258 from the stop codon in the TSP1 3'-UTR, involved in the stability by heat shock. Thus, the induction of TSP1 by heat shock may occur through a post-transcriptional mechanism.

3' Untranslated Regions↗
PubMed2002

Post-transcriptional regulation of hepatic NADPH-cytochrome P450 reductase by thyroid hormone: independent effects on poly(A) tail length and mRNA stability.

Thyroid hormone [triiodothyronine (T3)] positively regulates NADPH cytochrome P450 reductase (P450R) mRNA expression in rat liver, with P450R transcription initiation being a key regulated step. T3 is presently shown to have significant post-transcriptional effects on P450R expression. T3 increased the size of cytoplasmic P450R mRNA by approximately 105 nucleotides 12 h after T3 treatment, followed by a return to basal levels at 24 h. Primer extension analysis and Northern hybridization with 5'-untranslated region probes revealed no change in P450R mRNA 5' structure with T3 treatment. By contrast, RNase H analysis revealed a transient, T3-induced increase in P450R mRNA poly(A) tail, from approximately 100 to approximately 205 A. This increase in P450R polyadenylation, detectable in the nucleus 8 h after T3 treatment and in the cytoplasm at 12 h, was transient and was reversed by 16 h, when the T3-induced accumulation of cytoplasmic P450R mRNA was near maximal. Actinomycin D blocked the increase in P450R poly(A) tail and the induction of P450R mRNA, indicating a requirement for ongoing gene transcription for both T3 responses. T3 treatment destabilized P450R mRNA in rat liver in vivo, as shown by the T3-dependent 6-fold decrease in cytoplasmic P450R mRNA half-life, from a basal value of >or=16 h in uninduced liver to approximately 2.5 h, measured 24 h after T3 administration. These findings demonstrate that T3 increases nuclear polyadenylation of P450R RNA as a transient, early regulatory response and that this response is temporally dissociated from the subsequent decrease in cytoplasmic P450R mRNA stability.

3' Untranslated Regions↗
PubMed1995

Low temperature persistence of type I antifreeze protein is mediated by cold-specific mRNA stability.

In winter flounder, the levels of type I antifreeze protein (AFP) and its mRNA vary seasonally by as much as 1000-fold. Elevated levels in the fall are prompted by the loss of long day-lengths, while higher spring temperatures correlate with AFP clearance. We have investigated the role of temperature on AFP accumulation using transgenic Drosophila melanogaster by expressing multiple AFP genes under control of the heat-inducible hsp70 promoter. AFP and AFP mRNA persisted far longer in flies reared at 10 degrees C compared to 22 degrees C. This difference appears to be mediated by cold-specific mRNA stability since no such temperature effect was observed with either an endogenous heat-inducible mRNA or a constitutively expressed mRNA.

Animals↗
PubMed2003

The stem-loop region of the tobacco psbA 5'UTR is an important determinant of mRNA stability and translation efficiency.

Regulation of chloroplast gene expression involves networked and concerted interactions of nucleus-encoded factors with their target sites on untranslated regions (UTRs) of chloroplast transcripts. So far, only a few cis-acting elements within such 5'UTR sequences have been identified as functional determinants of mRNA stability and efficient translation in Chlamydomonas in vivo. In this study, we have used chloroplast transformation and site-directed mutagenesis to analyse the functions of the 5'UTRs of tobacco psbA and rbcL fused to the coding region of the reporter gene uidA. Various mutant versions of the psbA leader, as well as rbcL/psbA hybrid leader elements, were investigated. Our results showed a 1.5- to 3-fold decrease in uidA mRNA levels and a 1.5- to 6-fold reduction in uidA translation efficiency in all psbA 5'UTR stem-loop mutants generated by sequence deletions and base alterations. This indicates that the correct primary sequence and secondary structure of the psbA 5'UTR stem-loop are required for mRNA stabilisation and translation. The 5'-terminal segment of the rbcL 5'UTR did not enhance the stability or translational activity of chimeric uidA mRNA under the standard light-dark regime of 16 h light and 8 h dark. Stabilising effects were, however, observed when the cells were kept continuously in the dark. Possible reasons for the influence of the 5'UTR of the tobacco psbA on mRNA stability and translation efficiency are discussed.

5' Untranslated Regions↗
PubMed1991

Differential gene expression from the Escherichia coli atp operon mediated by segmental differences in mRNA stability.

The atp operon of Escherichia coli directs synthesis rates of protein subunits that are well matched to the requirements of assembly of the membrane-bound H(+)-ATPase (alpha 3 beta 3 gamma 1 delta 1 epsilon 1a1b2c10-15). Segmental differences in mRNA stability are shown to contribute to the differential control of atp gene expression. The first two genes of the operon, atpl and atpB, are rapidly inactivated at the mRNA level. The remaining seven genes are more stable. It has previously been established that the translational efficiencies of the atp genes vary greatly. Thus differential expression from this operon is achieved via post-transcriptional control exerted at two levels. Neither enhancement of translational efficiency nor insertion of repetitive extragenic palindromic (REP) sequences into the atplB intercistronic region stabilized atpl. We discuss the implications of these results in terms of the pathway of mRNA degradation and of the role of mRNA stability in the control of gene expression.

Base Sequence↗
PubMed2004

Cold induction of the Bacillus subtilis bkd operon is mediated by increased mRNA stability.

Recently it has been demonstrated that the ptb - bcd - buk - lpdV - bkdAA - bkdAB - bkdB operon ( bkdoperon) of Bacillus subtilis, which encodes the enzymes that catalyze the degradation of branched-chain amino acids, is inducible by a temperature downshift from 37 to 18 degrees C. Deamination and oxidative decarboxylation of isoleucine generates 2-methyl-butyryl-CoA, which serves as the precursor of anteiso-branched fatty acid species. Most probably, the induction of this operon upon cold shock ensures an increase in the content of anteiso-branched fatty acids in the membrane lipids at low temperature, thus permitting maintenance of membrane fluidity at lower temperatures. In the present study, we have analyzed the mechanism of cold induction of the bkd operon and of four further cold-inducible transcriptional units in B. subtilis. We demonstrate that cold induction of these genes is mediated by an increase in the stability of the corresponding mRNAs. None of the promoters that control the five transcriptional units analyzed is actually cold-inducible. Furthermore, the results of this study indicate that the 5' leader regions are not involved in the cold-induced stabilization of the mRNAs. The structural elements that enhance mRNA stability must therefore be restricted to the 3'-ends and/or the coding regions.

Bacillus subtilis↗
PubMed2003

Coupled mRNA stabilization and translational silencing of cyclooxygenase-2 by a novel RNA binding protein, CUGBP2.

Cyclooxygenase-2 (COX-2) expression is translationally silenced in epithelial cells undergoing radiation-induced apoptosis. CUGBP2, a predominantly nuclear protein, is also rapidly induced in response to radiation and translocates to the cytoplasm. Antisense-mediated suppression of CUGBP2 renders radioprotection through a COX-2-dependent prostaglandin pathway, providing an in vivo demonstration of translation inhibition activity for CUGBP2. CUGBP2 binds to two sets of AU-rich sequences (AREs) located within the first sixty nucleotides of the COX-2 3' untranslated region (3'UTR). Upon binding, CUGBP2 stabilizes a chimeric luciferase-COX-2 3'UTR mRNA but inhibits its translation. These findings identify a novel paradigm for RNA binding proteins in facilitating opposing functions of mRNA stability and translation inhibition and reveal a mechanism for inhibiting COX-2 expression in cancer cells.

3' Untranslated Regions↗