• ZFP36
• blood pressure
• hypertension
• smooth muscle contraction

• Animals
• Muscle, Smooth, Vascular/metabolism
• Mice
• Rats
• Blood Pressure/genetics
• Blood Pressure/physiology
• Hypertension/metabolism
• Hypertension/genetics
• Male
• Tristetraprolin/metabolism
• Tristetraprolin/genetics
• Muscle Contraction/genetics
• Muscle Contraction/physiology
• Angiotensin II/metabolism
• Humans
• RGS Proteins/genetics
• RGS Proteins/metabolism
• Disease Models, Animal
• Mice, Inbred C57BL

• 82270457 National Natural Science Foundation of China
• 82470499 National Natural Science Foundation of China
• 82200480 National Natural Science Foundation of China
• U21A20391 National Natural Science Foundation of China
• 82370343 National Natural Science Foundation of China
• ZR2024ZD23 Natural Science Foundation of Shandong Province
• 2021YFA1301102 National Key Research and Development Project of China
• tstp20240852 Taishan Scholar Foundation of Shandong Province
• National Natural Science Foundation of China
• Natural Science Foundation of Shandong Province
• Taishan Scholar Foundation of Shandong Province

• Colon cancer cell
• Cytotoxicity
• Gene expression
• Lipopolysaccharide

• Humans
• Lipopolysaccharides/pharmacology
• Endotoxins
• Colonic Neoplasms/genetics
• Gene Expression

• CRIS 6054-41000-103-00-D and 6054-41000-113-00-D Agricultural Research Service, United States

• CP: Metabolism
• CP: Molecular biology
• RNA-binding proteins
• growth factor signaling
• mRNA stability
• metabolism

• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism
• Signal Transduction
• Intercellular Signaling Peptides and Proteins/metabolism
• RNA Stability/genetics
• Tristetraprolin/genetics
• Tristetraprolin/metabolism

• P30 CA016042 NCI NIH HHS
• R01 AR070245 NIAMS NIH HHS
• R01 CA215185 NCI NIH HHS
• T32 HL069766 NHLBI NIH HHS

• 3′UTR diversity
• RNA alterations
• alternative polyadenylation
• alternative splicing
• cancer
• transcriptome

• Humans
• 3' Untranslated Regions/genetics
• RNA, Messenger/genetics
• Polyadenylation/genetics
• Transcriptome
• Alternative Splicing/genetics

Cottonseed contains many bioactive molecules including plant polyphenols. Cottonseed value might be increased by providing high-value bioactive polyphenols for improving nutrition and health. However, there was a lack of molecular evidence for cottonseed bioactivity in mammalian cells. One widely used method for evaluating the bioactivity of natural products is quantitative real-time-PCR (qPCR). The selection of stably expressed internal reference genes is a crucial task of qPCR assay for data analysis. The rationale for reference gene selection is that a lower standard deviation of the cycle of threshold (Cq) among the treatments indicates a more stable expression of the gene. The objective of this study was to select reference genes in human colon cancer cells (COLO 205) treated with cottonseed-derived gossypol and bioactive extracts along with bacterial endotoxin lipopolysaccharides (LPS). SYBR Green qPCR was used to analyze the mRNA levels of a wide range of biomarkers involved in glucose transport, lipid biosynthesis, inflammatory response, and cancer development. qPCR data (10,560 Cq values) were generated from 55 genes analyzed from 64 treatments with triplicate per treatment for each gene. The data showed that B-cell lymphoma 2 (Bcl2) mRNA was the most stable among the 55 mRNAs analyzed in the human colon cancer cells. Glyceraldehyde 3 phosphate dehydrogenase (Gapdh) and ribosome protein L32 (Rpl32) mRNAs were not good qPCR references for the colon cancer cells. These observations were consistent regardless of the treatment comparison between gossypol and LPS, glanded and glandless seed extracts, seed coat and kernel extracts, or treatment for 8 and 24 h. These results suggest that Bcl2 is a preferable reference gene for qPCR assays in human colon cancer cells treated with cottonseed-derived gossypol and bioactive extracts as well as LPS. The extensive qPCR results firmly support the conclusion that the Bcl2 gene is stably expressed at the mRNA level in the human colon cancer cells regardless of the treatment, suggesting that Bcl2 gene expression is not regulated at the mRNA level but at the post-transcriptional level. These results should facilitate studies designated to evaluate bioactivity on gene expression regulation by cottonseed molecules and other natural and synthetic molecules for nutrition and health uses.

• Animals
• Humans
• Cottonseed Oil/analysis
• Gossypol/pharmacology
• Gossypol/analysis
• Lipopolysaccharides/pharmacology
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/genetics
• Bacteria
• RNA, Messenger
• Mammals
• Proto-Oncogene Proteins c-bcl-2

Cotton plant provides economically important fiber and cottonseed, but cottonseed contributes 20% of the crop value. Cottonseed value could be increased by providing high value bioactive compounds and polyphenolic extracts aimed at improving nutrition and preventing diseases because plant polyphenol extracts have been used as medicinal remedy for various diseases. The objective of this study was to investigate the effects of cottonseed extracts on cell viability and gene expression in human colon cancer cells. COLO 225 cells were treated with ethanol extracts from glanded and glandless cottonseed followed by MTT and qPCR assays. Cottonseed extracts showed minor effects on cell viability. qPCR assay analyzed 55 mRNAs involved in several pathways including DGAT, GLUT, TTP, IL, gossypol-regulated and TTP-mediated pathways. Using BCL2 mRNA as the internal reference, qPCR analysis showed minor effects of ethanol extracts from glanded seed coat and kernel and glandless seed coat on mRNA levels in the cells. However, glandless seed kernel extract significantly reduced mRNA levels of many genes involved in glucose transport, lipid biosynthesis and inflammation. The inhibitory effects of glandless kernel extract on gene expression may provide a useful opportunity for improving nutrition and healthcare associated with colon cancer. This in turn may provide the potential of increasing cottonseed value by using ethanol extract as a nutrition/health intervention agent.

• apoptosis
• cell signalling

• biochemistry
• cancer
• plant sciences
• molecular medicine

• DSS
• IL-17
• RNA-binding protein
• TH17
• colitis
• mRNA decay
• tristetraprolin

• Animals
• Anti-Inflammatory Agents/pharmacology
• Antibodies, Neutralizing/pharmacology
• Colitis/chemically induced
• Colitis/immunology
• Colitis/metabolism
• Colitis/prevention & control
• Colon/drug effects
• Colon/immunology
• Colon/metabolism
• Colon/pathology
• Dermatitis/immunology
• Dermatitis/metabolism
• Dextran Sulfate
• Disease Models, Animal
• Humans
• Interleukin-17/blood
• Interleukin-17/genetics
• Jurkat Cells
• Mice, Inbred C57BL
• Mice, Knockout
• RNA Stability
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Signal Transduction
• Th17 Cells/drug effects
• Th17 Cells/immunology
• Th17 Cells/metabolism
• Tristetraprolin/deficiency
• Tristetraprolin/genetics
• Tristetraprolin/metabolism

• UL1 TR002345 NCATS NIH HHS
• R01 CA163808 NCI NIH HHS

Post-transcriptional regulation of gene expression plays a key role in cellular proliferation, differentiation, migration, and apoptosis. Increasing evidence suggests dysregulated post-transcriptional gene expression as an important mechanism in the pathogenesis of cancer. The tristetraprolin family of RNA-binding proteins (RBPs), which include Zinc Finger Protein 36 (ZFP36; commonly referred to as tristetraprolin (TTP)), Zinc Finger Protein 36 like 1 (ZFP36L1), and Zinc Finger Protein 36 like 2 (ZFP36L2), play key roles in the post-transcriptional regulation of gene expression. Mechanistically, these proteins function by binding to the AU-rich elements within the 3′-untranslated regions of their target mRNAs and, in turn, increasing mRNA turnover. The TTP family RBPs are emerging as key regulators of multiple biological processes relevant to cancer and are aberrantly expressed in numerous human cancers. The TTP family RBPs have tumor-suppressive properties and are also associated with cancer prognosis, metastasis, and resistance to chemotherapy. Herein, we summarize the various hallmark molecular traits of cancers that are reported to be regulated by the TTP family RBPs. We emphasize the role of the TTP family RBPs in the regulation of trait-associated mRNA targets in relevant cancer types/cell lines. Finally, we highlight the potential of the TTP family RBPs as prognostic indicators and discuss the possibility of targeting these TTP family RBPs for therapeutic benefits.

• RNA-binding proteins
• ZFP36
• post-transcriptional regulation
• tristetraprolin
• tumor suppressor

Background and objectives: The effectiveness of neoadjuvant therapy, which is commonly used for stage II-III rectal cancer (RC) treatment, is limited. Genes associated with the pathogenesis of RC could determine response to this treatment. Therefore, the aim of this study was to investigate the potential predictive value of VEGFA, COX2, HUR and CUGBP2 genes and the associations between post-treatment changes in gene expression and the efficacy of neoadjuvant therapy. Materials and Methods: Biopsies from RC and healthy rectal tissue of 28 RC patients were collected before neoadjuvant therapy and 6-8 weeks after neoadjuvant therapy. The expression levels of VEGFA, COX2, HUR, CUGBP2 genes were evaluated using a quantitative real-time polymerase chain reaction. Results: The results reveal a significantly higher expression of VEGFA, COX2 and HUR mRNA in RC tissue compared to healthy rectal tissue (p < 0.05), and elevated VEGFA gene expression in pre-treatment tissues was associated with a better response to neoadjuvant therapy based on T-stage downstaging (p < 0.05). The expression of VEGFA, HUR and CUGBP2 genes significantly decreased after neoadjuvant therapy (p < 0.05). Responders to treatment demonstrated a significantly stronger decrease of VEGFA and COX2 expression after neoadjuvant therapy than non-responders (p < 0.05). Conclusions: The findings of this study suggest that the pre-treatment VEGFA gene expression might have predictive value for the response to neoadjuvant therapy, while the post-treatment decrease in VEGFA and COX2 gene expression could indicate the effectiveness of neoadjuvant therapy in RC patients.

• COX2
• CUGBP2
• HUR
• VEGFA
• neoadjuvant therapy
• rectal cancer

Inflammatory activation of astroglia adds to the pathology of various neurological diseases. Astrocytes respond to microglia-derived cytokines such as interleukin-1α (IL-1α) with enhanced inflammatory signaling. This provokes pro-inflammatory gene expression of, among others, the eicosanoid-generating enzyme prostaglandin endoperoxide synthase 2 (Ptgs2). Whereas metabolic regulation of innate immune cell inflammatory responses is intensely studied, pathways related to how metabolism modulates inflammatory signaling in astrocytes are underexplored. Here, we examined how mitochondrial oxidative phosphorylation affects inflammatory responses towards IL-1α and tumor necrosis factor α in neonatal rat astrocytes. Blocking respiratory complex I and III or adenosine triphosphate (ATP) synthase did not affect activation of inflammatory signaling by IL-1α, but did elicit differential effects on inflammatory gene mRNA expression. Remarkably, mRNA and protein expression of Ptgs2 by IL-1α was consistently up-regulated when oxidative phosphorylation was inhibited. The increase of Ptgs2 resulted from mRNA stabilization. Mitochondrial inhibitors also increased IL-1α-triggered secretion of eicosanoids, such as prostaglandin E₂, prostaglandin F_2α, and 6-keto-prostaglandin F_1α, as assessed by liquid chromatography/mass spectrometry. Mechanistically, attenuating oxidative phosphorylation elevated adenosine monophosphate (AMP) and activated AMP-activated protein kinase (AMPK). AMPK silencing prevented Ptgs2 up-regulation by mitochondrial inhibitors, while AMPK activators recapitulated Ptgs2 mRNA stability regulation. Our data indicate modulation of astrocyte inflammatory responses by oxidative metabolism, with relevance towards eicosanoid production.

• astrocytes
• inflammation
• mitochondria
• prostaglandins

Over the last years, many microRNAs (miRNAs) have been identified that regulate the formation of bioactive lipid mediators such as prostanoids and leukotrienes. Many of these miRNAs are involved in complex regulatory circuits necessary for the fine-tuning of biological functions including inflammatory processes or cell growth. A better understanding of these networks will contribute to the development of novel therapeutic strategies for the treatment of inflammatory diseases and cancer. In this review, we provide an overview of the current knowledge of miRNA regulation in eicosanoid pathways with special focus on novel miRNA functions and regulatory circuits of leukotriene and prostaglandin biosynthesis.

• eicosanoids
• inflammation
• microRNA
• new miRNA functions
• prostaglandins

Trans-acting factors controlling mRNA fate are critical for the post-transcriptional regulation of inflammation-related genes, as well as for oncogene and tumor suppressor expression in human cancers. Among them, a group of RNA-binding proteins called “Adenylate-Uridylate-rich elements binding proteins” (AUBPs) control mRNA stability or translation through their binding to AU-rich elements enriched in the 3’UTRs of inflammation- and cancer-associated mRNA transcripts. AUBPs play a central role in the recruitment of target mRNAs into small cytoplasmic foci called Processing-bodies and stress granules (also known as P-body/SG). Alterations in the expression and activities of AUBPs and P-body/SG assembly have been observed to occur with colorectal cancer (CRC) progression, indicating the significant role AUBP-dependent post-transcriptional regulation plays in controlling gene expression during CRC tumorigenesis. Accordingly, these alterations contribute to the pathological expression of many early-response genes involved in prostaglandin biosynthesis and inflammation, along with key oncogenic pathways. In this review, we summarize the current role of these proteins in CRC development. CRC remains a major cause of cancer mortality worldwide and, therefore, targeting these AUBPs to restore efficient post-transcriptional regulation of gene expression may represent an appealing therapeutic strategy.

• Colorectal cancer
• Adenylate-Uridylate-rich element-binding proteins
• Oncogenes
• Tumor suppressors
• Post-transcriptional regulation

Genetic loss or mutations in tumor suppressor genes promote tumorigenesis. The prospective tumor suppressor tristetraprolin (TTP) has been shown to negatively regulate tumorigenesis through destabilizing the messenger RNAs of critical genes implicated in both tumor onset and tumor progression. Regulation of TTP has therefore emerged as an important issue in tumorigenesis. Similar to other tumor suppressors, TTP expression is frequently downregualted in various human cancers, and its low expression is correlated with poor prognosis. Additionally, disruption in the regulation of TTP by various mechanisms results in the inactivation of TTP protein or altered TTP expression. A recent study showing alleviation of Myc-driven lymphomagenesis by the forced expression of TTP has shed light on new therapeutic avenues for cancer prevention and treatment through the restoration of TTP expression. In this review, we summarize key oncogenes subjected to the TTP-mediated mRNA degradation, and discuss how dysregulation of TTP can contribute to tumorigenesis. In addition, the control mechanism underlying TTP expression at the posttranscriptional and posttranslational levels will be discussed.

• adenosine and uridine-rich elements (AREs)
• posttranscriptional regulation
• tristetraprolin (TTP)
• tumorigenesis

• Animal model
• Dog
• RNA sequencing
• Transitional cell carcinoma

Cyclooxygenase-2 (COX-2), with its main antifibrotic metabolite PGE₂, is regarded as an antifibrotic gene. Repressed COX-2 expression and deficient PGE₂ have been shown to contribute to the activation of lung fibroblasts and excessive deposition of collagen in pulmonary fibrosis. We have previously demonstrated that COX-2 expression in lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) is epigenetically silenced and can be restored by epigenetic inhibitors. This study aimed to investigate whether COX-2 downregulation induced by the profibrotic cytokine transforming growth factor-β1 (TGF-β1) in normal lung fibroblasts could be prevented by epigenetic inhibitors. We found that COX-2 protein expression and PGE₂ production were markedly reduced by TGF-β1 and this was prevented by the pan-histone deacetylase inhibitor suberanilohydroxamic acid (SAHA) and to a lesser extent by the DNA demethylating agent Decitabine (DAC), but not by the G9a histone methyltransferase (HMT) inhibitor BIX01294 or the EZH2 HMT inhibitor 3-deazaneplanocin A (DZNep). However, chromatin immunoprecipitation assay revealed that the effect of SAHA was unlikely mediated by histone modifications. Instead 3′-untranslated region (3′-UTR) luciferase reporter assay indicated the involvement of post-transcriptional mechanisms. This was supported by the downregulation by SAHA of the 3′-UTR mRNA binding protein TIA-1 (T-cell intracellular antigen-1), a negative regulator of COX-2 translation. Furthermore, TIA-1 knockdown by siRNA mimicked the effect of SAHA on COX-2 expression. These findings suggest SAHA can prevent TGF-β1-induced COX-2 repression in lung fibroblasts post-transcriptionally through a novel TIA-1-dependent mechanism and provide new insights into the mechanisms underlying its potential antifibrotic activity.

Unlabelled Table

•

The HDAC inhibitor SAHA upregulates the expression of the antifibrotic gene COX-2 post-transcriptionally.

• Cyclooxygenase 2 (COX-2)
• Histone deacetylase inhibitor
• Post-transcriptional regulation, epigenetics
• Pulmonary fibrosis
• Transforming growth factor β1 (TGF-β1)

• Alternative splicing
• Decay
• Disease
• Exosome
• Neurodegeneration
• RNA
• Stress granule
• Transport

• RNA binding proteins
• mRNA fate
• post-transcriptional regulation
• stability
• translation

IFN-γ-producing cytotoxic T lymphocytes are essential for host defense against viral infection and cancer. Here we show that the RNA-binding tristetraprolin, encoded by Zfp36, is needed for CD8⁺ T-cell production of IFN-γ in vivo. When activated in vitro, however, IFN-γ production by naive wild type and tristetraprolin-deficient CD8⁺ T-cells is comparable. IL-27 is overproduced by tristetraprolin-deficient macrophages and increased systemically in tristetraprolin-deficient mice. Tristetraprolin suppresses IL-27 production by promoting p28 mRNA degradation. Importantly, deletion of IL-27 receptor WSX-1 in tristetraprolin-deficient mice (WSX-1/tristetraprolin double knockout) leads to a reduction in cytotoxic T lymphocyte numbers. Moreover, tumor growth is accelerated, not only in tristetraprolin-deficient mice after cytotoxic T lymphocyte depletion, but also in WSX-1/tristetraprolin double knockout mice, with substantial reduction in the number of tumor cytotoxic T lymphocytes. This study describes a regulatory pathway for IL-27 expression and cytotoxic T lymphocyte function mediated by tristetraprolin, contributing to regulation of antitumour immunity.

IL-27 is one of a number of cytokines that can induce antitumour CD8⁺ T cell responses. Here the authors show that TTP, encoded by Zfp36, degrades p28 to inhibit IL-27 production by macrophages and is thereby a negative regulator of the antitumour response.

In many different cell types, pro-inflammatory agonists induce the expression of cyclooxygenase 2 (COX-2), an enzyme that catalyzes rate-limiting steps in the conversion of arachidonic acid to a variety of lipid signaling molecules, including prostaglandin E₂ (PGE₂). PGE₂ has key roles in many early inflammatory events, such as the changes of vascular function that promote or facilitate leukocyte recruitment to sites of inflammation. Depending on context, it also exerts many important anti-inflammatory effects, for example increasing the expression of the anti-inflammatory cytokine interleukin 10 (IL-10), and decreasing that of the pro-inflammatory cytokine tumor necrosis factor (TNF). The tight control of both biosynthesis of, and cellular responses to, PGE₂ are critical for the precise orchestration of the initiation and resolution of inflammatory responses. Here we describe evidence of a negative feedback loop, in which PGE₂ augments the expression of dual specificity phosphatase 1, impairs the activity of mitogen-activated protein kinase p38, increases the activity of the mRNA-destabilizing factor tristetraprolin, and thereby inhibits the expression of COX-2. The same feedback mechanism contributes to PGE₂-mediated suppression of TNF release. Engagement of the DUSP1-TTP regulatory axis by PGE₂ is likely to contribute to the switch between initiation and resolution phases of inflammation.

• COX-2
• Endothelial cells
• Glioblastoma
• Olive oil
• PGE(2)
• TNF-α

The RNA-binding protein tristetraprolin (TTP) promotes rapid decay of mRNAs bearing 3' UTR AU-rich elements (ARE). In many cancer types, loss of TTP expression is observed allowing for stabilization of ARE-mRNAs and their pathologic overexpression. Here we demonstrate that histone deacetylase (HDAC) inhibitors (Trichostatin A, SAHA and sodium butyrate) promote TTP expression in colorectal cancer cells (HCA-7, HCT-116, Moser and SW480 cells) and cervix carcinoma cells (HeLa). We found that HDAC inhibitors-induced TTP expression, promote the decay of COX-2 mRNA, and inhibit cancer cell proliferation. HDAC inhibitors were found to promote TTP transcription through activation of the transcription factor Early Growth Response protein 1 (EGR1). Altogether, our findings indicate that loss of TTP in tumors occurs through silencing of EGR1 and suggests a therapeutic approach to rescue TTP expression in colorectal cancer.

• COX-2
• HDAC
• TTP
• colon cancer
• post-transcriptional regulation

• Butyric Acid/pharmacology
• Cell Line, Tumor
• Colorectal Neoplasms/metabolism
• Cyclooxygenase 2/genetics
• Cyclooxygenase 2/metabolism
• Early Growth Response Protein 1/metabolism
• Epigenesis, Genetic
• Histone Deacetylase Inhibitors/pharmacology
• Humans
• Hydroxamic Acids/pharmacology
• RNA, Messenger/metabolism
• Tristetraprolin/genetics
• Tristetraprolin/metabolism
• Vorinostat

• P30 CA168524 NCI NIH HHS
• R01 CA134609 NCI NIH HHS

• AU-rich elements
• mRNA decay
• mouse embryonic fibroblasts
• tumor necrosis factor

• Cytokines
• Inflammation markers
• Suicide

• Cyclooxygenase 2
• RNA stability
• Smad3
• Transforming growth factor beta
• Tristetraprolin

• Endoribonuclease
• Mitogenic Stimuli
• Post-transcriptional Regulation
• RNA-binding Protein
• RNase L
• Serum-response Factor
• Transcription Regulation
• Transcriptional Regulation
• Tristetraprolin
• mRNA Decay

Alternative polyadenylation (APA) is a widespread mechanism that contributes to the sophisticated dynamics of gene regulation. Approximately 50% of all protein-coding human genes harbor multiple polyadenylation (PA) sites; their selective and combinatorial use gives rise to transcript variants with differing length of their 3′ untranslated region (3′UTR). Shortened variants escape UTR-mediated regulation by microRNAs (miRNAs), especially in cancer, where global 3′UTR shortening accelerates disease progression, dedifferentiation and proliferation. Here we present APADB, a database of vertebrate PA sites determined by 3′ end sequencing, using massive analysis of complementary DNA ends. APADB provides (A)PA sites for coding and non-coding transcripts of human, mouse and chicken genes. For human and mouse, several tissue types, including different cancer specimens, are available. APADB records the loss of predicted miRNA binding sites and visualizes next-generation sequencing reads that support each PA site in a genome browser. The database tables can either be browsed according to organism and tissue or alternatively searched for a gene of interest. APADB is the largest database of APA in human, chicken and mouse. The stored information provides experimental evidence for thousands of PA sites and APA events. APADB combines 3′ end sequencing data with prediction algorithms of miRNA binding sites, allowing to further improve prediction algorithms. Current databases lack correct information about 3′UTR lengths, especially for chicken, and APADB provides necessary information to close this gap.

Database URL:http://tools.genxpro.net/apadb/

• 3' Untranslated Regions
• AU Rich Elements/genetics
• Base Sequence
• Cell Line
• Gene Expression Regulation
• Humans
• Molecular Sequence Data
• Protein Biosynthesis
• RNA Stability/drug effects
• RNA Stability/genetics
• RNA, Messenger/genetics
• Tristetraprolin/genetics
• Tristetraprolin/metabolism
• Tumor Necrosis Factor-alpha/genetics
• Tumor Necrosis Factor-alpha/metabolism
• Zinc Fingers/genetics

• ZIA ES090080 Intramural NIH HHS
• ZIA ES090080-15 Intramural NIH HHS

• AU-rich element
• Butyrate Response Factor
• Tristetraprolin
• mRNA decay
• post-transcriptional regulation

• Adult
• CD4-Positive T-Lymphocytes/metabolism
• CD8-Positive T-Lymphocytes/metabolism
• Chemokine CCL5/pharmacology
• China
• Cytokines/metabolism
• DNA Primers/genetics
• Female
• Gene Expression Regulation/drug effects
• Gene Expression Regulation/immunology
• Gene Knockdown Techniques
• Hepatitis B/complications
• Hepatitis B/metabolism
• Hepatitis B Surface Antigens/metabolism
• Humans
• Inflammation/drug therapy
• Inflammation/etiology
• Inflammation/immunology
• Interleukin-8/pharmacology
• Leukocytes, Mononuclear/metabolism
• Male
• Middle Aged
• RNA, Small Interfering/genetics
• Real-Time Polymerase Chain Reaction
• Tristetraprolin/genetics
• Tristetraprolin/metabolism

• 3' Untranslated Regions
• AT Rich Sequence
• Animals
• Base Sequence
• Cell Culture Techniques
• Cell Line
• Enzyme Activation/drug effects
• Gene Expression Regulation/drug effects
• Humans
• Mice
• Mice, Knockout
• Mitogens/pharmacology
• Molecular Sequence Data
• Organ Specificity/genetics
• Protein Processing, Post-Translational
• Proto-Oncogene Proteins c-pim-1/genetics
• Proto-Oncogene Proteins c-pim-1/metabolism
• RNA Stability
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Response Elements
• Transcription, Genetic/drug effects
• Tristetraprolin/genetics
• Tristetraprolin/metabolism

• R01 AI077556 NIAID NIH HHS
• R01 CA102428 NCI NIH HHS
• R56 CA102428 NCI NIH HHS
• CA102428 NCI NIH HHS

• Binding Sites
• Cyclooxygenase 2/genetics
• DNA-Binding Proteins/physiology
• Endothelial Cells/metabolism
• Fever
• Gene Expression Regulation
• Heat Shock Transcription Factors
• Hot Temperature
• Humans
• Promoter Regions, Genetic
• Transcription Factors/physiology
• Transcription, Genetic

• Animals
• Apoptosis/genetics
• Base Sequence
• Biopsy
• Carcinoma, Hepatocellular/enzymology
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Cell Line, Tumor
• Cell Proliferation
• Cell Transformation, Neoplastic/genetics
• Cell Transformation, Neoplastic/pathology
• Cyclooxygenase 2/genetics
• Cyclooxygenase 2/metabolism
• Down-Regulation
• ELAV Proteins/metabolism
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms/enzymology
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Mice
• Mice, Nude
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Molecular Sequence Data
• Protein Biosynthesis/genetics
• Protein Stability
• RNA Stability/genetics
• RNA, Messenger/genetics
• RNA, Messenger/metabolism