Expression Of Certain microRNAs Research Articles

Abstract P5-08-51: SIAH2 protein expression is inversely correlated with the ER status and outcome to tamoxifen therapy in metastatic breast cancer patients

Abstract Introduction: In a previous study we observed a positive correlation between Seven in Absentia Homolog 2 (SIAH2) and Estrogen Receptor (ER) mRNA levels. Additionally, high SIAH2 mRNA levels were related to a favorable progression-free survival (PFS) after first-line tamoxifen. In contrast, others showed high SIAH2 protein levels in ER-negative breast cancer associated with an unfavorable relapse-free survival. In this study, we investigated the above discrepancy between SIAH2 protein and mRNA findings and evaluated the prognostic and predictive value of SIAH2 protein in breast cancer patients. Patients and methods: Tissue microarrays (TMAs) of formalin-fixed, paraffin-embedded primary breast tumors were immunohistochemically stained for SIAH2 protein. The TMAs contained core specimens of 759 patients with early disease and of 245 ER-positive patients with advanced disease treated with first-line tamoxifen. SIAH2 protein staining was scored for its intensity and proportion positive cells and subsequently evaluated for its relationship with metastasis-free survival (MFS) and PFS in uni- and multivariate analyses including traditional prognostic or predictive factors, respectively. Results: The proportion SIAH2-positive cells had a relationship with MFS and PFS, whereas staining intensity and a previous described score for SIAH2 combining intensity and proportion were not related with clinical outcome. Based on these results, tumors with more than 20% positive cells were considered as SIAH2-positive. In early disease, 267 patients (35%) had SIAH2-positive tumors, which were further characterized by decreased expression of ER at protein and mRNA levels (P <0.001 and P = 0.003, respectively). These SIAH2-positive tumors correlated with significant unfavorable MFS in lymph node negative, ER-positive breast cancer patients, but only in univariate analysis. In advanced disease, 86 patients (35%) had SIAH2-positive tumors which was associated with an unfavorable PFS after first-line tamoxifen in both uni- and multivariate analyses (HR = 1.45; 95% CI, 1.07 to 1.96; P = 0.015). Conclusions: SIAH2 protein expression is especially observed in ER-negative tumors and has no additional prognostic value in breast cancer. The proportion SIAH2-positive cells in ER-positive tumors can be used as biomarker to predict tamoxifen treatment failure in breast cancer patients with advanced disease. Future studies should establish if expression of certain microRNAs explain the observed discrepancy in SIAH2 mRNA and protein levels. Citation Format: van der Willik KD, Timmermans MM, Look MP, Reijm EA, van Deurzen CHM, den Bakker MA, Westenend PJ, Martens JWM, Berns EMJJ, Jansen MPHM. SIAH2 protein expression is inversely correlated with the ER status and outcome to tamoxifen therapy in metastatic breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-51.

0109: Is there a differential expression of selected microRNAs depending on stent’s type and length one month after coronary angioplasty?

Stent thrombosis is a serious, although rare, complication of percutaneous coronary intervention (PCI). Some data from randomized trials indicate a higher risk for drug- eluting stents (DES) thrombosis. Furthermore, it has been shown that the most powerful histological predictor of stent thrombosis was endothelial coverage and that reendothelialization was delayed after implantation of first-generation DES compared with baremetal stents (BMS) as from the first month after PCI. We do not have yet simple blood test biomarkers that could reflect the ongoing process of stent reendothelialization. MicroRNAs are small, endogenous, noncoding RNAs, easily detectable in plasma, involved in a variety of cellular processes via suppression of specific target mRNAs and could be such biomarkers. Some of them have been linked to endothelial function and reendothelialization in animal or in vitro studies. We hypothesized that the expression of certain microRNAs was informative of stent endothelialization. We therefore sought beforehand to determine wether stent type and stent length could influence the expression of candidate microRNAs in human peripheral blood. Between July 2008 and December 2013, all patients who underwent coronary angioplasty in our centre were asked to attend a systematic consultation one month after revascularization for blood sampling. Sixty patients with a single-vessel disease meeting over twenty clinical, biological, echocardiographic and angiographic criteria were selected: 30 with a BMS and 30 with a DES, with a balanced ratio of short (≤15mm) and long (>15mm) stents in each group. Twenty eight microRNAs were chosen based on a review of literature. Their expression was measured using qRT-PCR in plasma samples collected at one month. Levels were normalized to cel-miR-39 and compared between the two groups of patients. The results are currently under analysis (table next page).

Therapeutic potential of Hibiscus sabdariffa: A review of the scientific evidence

Abstract Background and objective Infusion of Hibiscus sabdariffa ( H. sabdariffa ) is a very popular drink in many parts of the world. Its phytochemical composition is associated to antioxidant, hypotensive, and antiatherosclerotic effects. However, the molecular mechanisms involved in these processes are not well known. The aim of this review was to report the scientific evidence supporting that regular use of H. sabdariffa decreases oxidative stress, atherosclerosis, lipid profile, and blood pressure. Materials and methods A search of recent publications was made in the following specialized electronic databases: Elsevier Journal, SciELO, FSTA, Science Direct, Springer Link, and NCBI. Results of research conducted in clinical trials in humans and in animal models and cell cultures were recorded. Keywords used included H. sabdariffa , oxidative stress, polyphenols, hypertension, atherosclerosis, and lipid profile. Results Results of the different articles suggested a possible therapeutic effect of H. sabdariffa extracts on oxidative stress, lipid profile, hypertension, and atherosclerosis thanks to its composition rich in phenolic compounds. Anthocyanins significantly decrease LDL oxidation, inhibit adipogenesis by regulating adipogenic signaling pathways and transcription factors, and modulate gene expression of certain microRNAs. No adverse events or side effects were reported. Conclusions Further more homogeneous, placebo-controlled studies in humans are needed to state that H. sabdariffa has therapeutic efficacy in humans.

Potencial terapéutico del Hibiscus sabdariffa: una revisión de las evidencias científicas

Background and objectiveInfusion of Hibiscus sabdariffa (H. sabdariffa) is a very popular drink in many parts of the world. Its phytochemical composition is associated to antioxidant, hypotensive, and antiatherosclerotic effects. However, the molecular mechanisms involved in these processes are not well known. The aim of this review was to report the scientific evidence supporting that regular use of H. sabdariffa decreases oxidative stress, atherosclerosis, lipid profile, and blood pressure. Material and methodsA search of recent publications was made in the following specialized electronic databases: Elsevier Journal, SciELO, FSTA, Science Direct, Springer Link, and NCBI. Results of research conducted in clinical trials in humans and in animal models and cell cultures were recorded. Keywords used included Hibiscus sabdariffa, oxidative stress, polyphenols, hypertension, atherosclerosis, and lipid profile. ResultsResults of the different articles suggested a possible therapeutic effect of H. sabdariffa extracts on oxidative stress, lipid profile, hypertension, and atherosclerosis thanks to its composition rich in phenolic compounds. Anthocyanins significantly decrease LDL oxidation, inhibit adipogenesis by regulating adipogenic signaling pathways and transcription factors, and modulate gene expression of certain microRNAs. No adverse events or side effects were reported. ConclusionsFurther more homogeneous, placebo-controlled studies in humans are needed to state that H. sabdariffa has therapeutic efficacy in humans.

Downregulation of miR-183 inhibits apoptosis and enhances the invasive potential of endometrial stromal cells in endometriosis

Endometriosis is a common gynecological disease, yet its pathogenesis remains poorly understood. Recent studies have demonstrated that the aberrant expression of certain microRNAs (miRNAs) may correlate with the development and progression of endometriosis. In this study, we profiled several differentially expressed miRNAs in the normal, eutopic and ectopic endometrium by miRNA microarray screening analysis, among which, miR-183 was found to be downregulated in the ectopic and eutopic tissues, and the result was further confirmed by real-time PCR (qPCR). Functional analysis indicated that miR-183 plays a promotional role in endometrial stromal cell (ESC) apoptosis and has a negative regulatory impact on the invasive ability of cells, although it has no effect on ESC proliferation. Ovarian steroids (17β-estradiol and progesterone) and inflammatory factors (tumor necrosis factor-α and interleukin-6) decreased the expression of miR-183 in the ESCs. This regulatory function may further manifest the growth and invasive potential of ESCs by altering the expression of miR-183. These findings suggest that the downregulation of miR-183 expression is involved in the development and progression of endometriosis.

Gene expression and regulation in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. Genome-wide (GW) association studies have identified more than 40 disease-associated loci, together accounting for only 10-20% of disease heritability. Gene expression represents the intermediate phenotype between DNA and disease phenotypic variation, and provides insights regarding genetic and epigenetic effects. We review data on gene expression and regulation in SLE by our group and other investigators. Systematic PubMed search for GW expression studies in SLE published since the year 2000. Deregulation of genes involved in type I interferon signaling is a consistent finding in the peripheral blood of active and severe SLE patients. Upregulation of granulocyte-specific transcripts especially in bone marrow mononuclear cells (BMMCs), and of myeloid lineage transcripts in lupus nephritis, provide evidence for pathogenic role of these cells. Gene network analysis in BMMCs identified central gene regulators which could represent therapeutic targets and a high similarity between SLE and non-Hodgkin lymphoma providing a molecular basis for the reported association of the two diseases. Gene expression abnormalities driven by deregulated expression of certain microRNAs in SLE contribute to interferon production, T- and B-cell hyperactivity, DNA hypomethylation, and defective tissue response to injury. Methylation arrays have revealed alterations in white blood cell DNA methylation in SLE suggesting an important role of epigenetics and the environment. Gene expression studies have contributed to the characterization of pathogenic processes in SLE. Integrated approaches utilizing genetic variation, transcriptome and epigenome profiling will facilitate efforts towards a molecular-based disease taxonomy.

Suppression of Induced microRNA-15b Prevents Rapid Loss of Cardiac Function in a Dicer Depleted Model of Cardiac Dysfunction

BackgroundDicer endonuclease, critical for maturation of miRNAs, is depleted in certain forms of cardiomyopathy which results in differential expression of certain microRNAs. We sought to elucidate the mechanisms underlying the rapid loss of cardiac function following cardiac-specific Dicer depletion in adult mice.ResultsConditional Dicer deletion in the adult murine myocardium demonstrated compromised heart function, mitochondrial dysfunction and oxidant stress. Elevated miR-15b was observed as an early response to Dicer depletion and was found to silence Pim-1 kinase, a protein responsible for maintaining mitochondrial integrity and function. Anti-miRNA based suppression of induced miRNA-15b rescued the function of Dicer-depleted adult heart and attenuated hypertrophy.ConclusionsAnti-miRNA based suppression of inducible miRNA-15b can prevent rapid loss of cardiac function in a Dicer-depleted adult heart and can be a key approach worthy of therapeutic consideration.

Abstract LB-106: A novel TCL1-Tg:p53−/− mouse model of human CLL

Abstract Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the United States and Europe. CLL patients with loss of p53 due to chromosome 17p deletion often exhibit more malignant disease phenotype, are refractory to standard treatment, and have poor clinical outcomes. Although there are several mouse models that resemble the chronic disease processes of CLL, no animal model has been reported that mimic the aggressive disease phenotype of CLL with loss of p53. To facilitate the investigation of the biology of aggressive CLL with loss of p53 and the underlying mechanisms, we generated a mouse model with Eu-TCL1-Tg:p53−/− genotype by crossing the Eu-TCL1-Tg mice with p53 knockout mice. The Eu-TCL1-Tg:p53−/- mice developed CLL disease at 3-4 months, significantly earlier than the parental Eu-TCL1-Tg mice that developed CLL disease at 8-12 months. Flow cytometry analysis showed that the IgM+/CD5+ cell population appeared in the peritoneal cavity, bone marrow, and the spleens of Eu-TCL1-Tg:p53−/- mice significantly earlier than that of the parental Eu-TCL1-Tg mice. Massive infiltration and accumulation of leukemia cells were found in the spleen, liver, and peritoneal cavity. In vitro study showed that the leukemia cells isolated from the Eu-TCL1-Tg:p53−/- mice were more resistant to fludarabine treatment than the leukemia cells isolated from spleens of TCL1-Tg mice. Interestingly, TUNEL assay revealed that there was higher apoptotic cell death found in the TCL1-Tg spleen tissue compared to the spleens of the Eu-TCL1-Tg:p53−/- mice, suggesting that the loss of p53 compromises the apoptotic process in vivo, and this might in part explain the drug resistant phenotype of CLL cells with 17p deletion. Further molecular analysis showed that the expression of MCL-1, a key survival molecule for CLL, was significantly increased at the mRNA and protein levels in the leukemia cells isolated from Eu-TCL1-Tg:p53−/- mice, which seemed to be associated with the abnormal expression of certain microRNAs including miR15a and miR-16. Overall, the Eu-TCL1-Tg:p53−/- mice display a disease phenotypes that resemble human CLL with 17p deletion, and represent a useful animal model for mechanistic study as well as evaluation of in vivo therapeutic efficacy of anti-CLL agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-106. doi:1538-7445.AM2012-LB-106

Expression of microRNAs, miR‐21, miR‐31, miR‐122, miR‐145, miR‐146a, miR‐200c, miR‐221, miR‐222, and miR‐223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance

MicroRNAs are a class of non-coding molecules found to regulate a variety of cellular functions in health and disease. Dysregulation of microRNAs is involved in liver disease, especially hepatocarcinogenesis. Since primary hepatic malignancies are typically characterized by late diagnosis, frequent recurrence, and poor response to adjuvant therapy, there is a need for the discovery of novel biomarkers in order to achieve earlier diagnosis, predict tumor aggressiveness and response to adjuvant therapy. The purpose of this study is to evaluate the expression of certain microRNAs (miR-21, -31, -122, -145, -146a, - 200c, -221, -222 and -223) in patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as to assess their prognostic significance. Micro-RNA expression was assessed by reverse transcription and real-time PCR (RT-PCR). Clinicopathological data and survival rates were retrieved and analyzed. According to our results, miR-21, miR-31, miR-122, miR-221, miR-222 were significantly up-regulated in HCC tissues, whereas miR-145, miR-146a, miR-200c, and miR-223 were found to be down-regulated. Concerning ICC samples, miR-21, miR-31, and miR-223 were found to be over-expressed, whereas miR-122, miR-145, miR-200c, miR-221, and miR-222 were down-regulated. Additionally, expression of miR-21, miR-31, miR-122, and miR-221 in HCC correlated with cirrhosis, while miR-21 and miR-221 associated with tumor stage and poor prognosis. In ICC tissues, miR-21, miR-31, and miR-223 were found to be over-expressed, but no correlation with clinicopathological features was found.

Suppression of microRNA-29 Expression by TGF-β1 Promotes Collagen Expression and Renal Fibrosis

Synthesis and deposition of extracellular matrix (ECM) within the glomerulus and interstitium characterizes renal fibrosis, but the mechanisms underlying this process are incompletely understood. The profibrotic cytokine TGF-β1 modulates the expression of certain microRNAs (miRNAs), suggesting that miRNAs may have a role in the pathogenesis of renal fibrosis. Here, we exposed proximal tubular cells, primary mesangial cells, and podocytes to TGF-β1 to examine its effect on miRNAs and subsequent collagen synthesis. TGF-β1 reduced expression of the miR-29a/b/c/family, which targets collagen gene expression, and increased expression of ECM proteins. In both resting and TGF-β1-treated cells, ectopic expression of miR-29 repressed the expression of collagens I and IV at both the mRNA and protein levels by targeting the 3'untranslated region of these genes. Furthermore, we observed low levels of miR-29 in three models of renal fibrosis representing early and advanced stages of disease. Administration of the Rho-associated kinase inhibitor fasudil prevented renal fibrosis and restored expression of miR-29. Taken together, these data suggest that TGF-β1 inhibits expression of the miR-29 family, thereby promoting expression of ECM components. Pharmacologic modulation of these miRNAs may have therapeutic potential for progressive renal fibrosis.

MicroRNA‐21 expression in neonatal blood associated with antenatal immunoglobulin E production and development of allergic rhinitis

The prevalence of allergic diseases has increased in the past decades. It is unknown whether expression of certain microRNAs (miRNAs) in neonatal leucocytes is correlated to IgE production and/or allergic diseases. This study investigated the association of miRNA expression in neonatal leucocytes with cord blood IgE (CBIgE) elevation and development of allergic disease. We screened for the expression of a panel of 157 miRNAs in mononuclear leucocytes from human umbilical cord blood (CB) samples with elevated CBIgE and tracked the association of down-regulated miRNA expression to the miRNA-targeted gene expression and to children with allergic rhinitis (AR). Among the initial screen of 10 CB samples with elevated CBIgE, expression of eight of the 157 miRNAs was low. Of these eight down-expressed miRNAs, three remained down-regulation in a validation with other 20 CB samples, and two of the three miRNAs, miR-21 and miR-126, were significantly lower in monocytes from AR children. Further analysis of mRNA expression of the miR-21-targeted genes identified that TGFBR2 expression on monocytes was significantly up-regulated in CB with elevated CBIgE, and in AR patients. Transfection of miR-21 precursor into monocytes from patients with AR increased miR-21 expression and decreased TGFBR2 expression. This study demonstrated the first in the literature that lower miR-21 expression in CB and increased TGFBR2 expression is associated with antenatal IgE production and development of AR.

Abstract 4033: MiR-21 upregulation in breast cancer cells leads to PTEN loss and Herceptin resistance

Abstract MicroRNAs (miRNA) are a class of small 22-nucleotides endogenous non-coding RNAs which serve as regulators of gene expression by targeting specific messenger RNAs (mRNA). Aberrant expression of certain microRNAs can lead to therapeutic drug resistance, such as Cisplatin resistance by miR-214 targeting PTEN. Our lab previously found that PTEN loss confers Herceptin resistance in ErbB2-overexpressing breast cancers. Other studies in hepatocellular carcinoma have shown that miR-21 targets the 3′UTR of PTEN mRNA leading to downregulation of PTEN protein levels. Based on these findings, we hypothesized that overexpression of miR-21 may confer Herceptin resistance in breast cancer patients by downregulation of PTEN. To test this hypothesis, mir-21 and/or control miRNA were transiently transfected and expressed in ErbB2-overexpressing AU565 and SKBr3 breast cancer cell lines, followed by Herceptin treatment. We found that cells with increased miR-21 had reduced PTEN expression and were significantly more resistant to Herceptin treatment versus control miRNA transfected cells. Conversely, when we knocked down miR-21 in high ErbB2 expressing BT474 cells, the cells showed increased PTEN expression and became more sensitive to Herceptin treatment versus control miRNA transfected cells. To determine the clinical relevance of our findings, we detected miR-21 level in patients’ breast cancers with ErbB2 expression that were treated with Herceptin and we found that high miR-21 level significantly correlated with patients’ poor response to Herceptin treatment and disease progression. We are currently identifying other targets of miR-21 to better understand the mechanisms of miR-21 mediated-Herceptin resistance, which may provide new insight on how to overcome Herceptin resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4033.

E-Cadherin Expression Is Regulated by miR-192/215 by a Mechanism That Is Independent of the Profibrotic Effects of Transforming Growth Factor-β

OBJECTIVEIncreased deposition of extracellular matrix (ECM) within the kidney is driven by profibrotic mediators including transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF). We investigated whether some of their effects may be mediated through changes in expression of certain microRNAs (miRNAs).RESEARCH DESIGN AND METHODSProximal tubular cells, primary rat mesangial cells, and human podocytes were analyzed for changes in the expression of key genes, ECM proteins, and miRNA after exposure to TGF-β (1–10 ng/μl). Tubular cells were also infected with CTGF-adenovirus. Kidneys from diabetic apoE mice were also analyzed for changes in gene expression and miRNA levels.RESULTSTGF-β treatment was associated with morphologic and phenotypic changes typical of epithelial-mesenchymal transition (EMT) including increased fibrogenesis in all renal cell types and decreased E-cadherin expression in tubular cells. TGF-β treatment also modulated the expression of certain miRNAs, including decreased expression of miR-192/215 in tubular cells, mesangial cells, which are also decreased in diabetic kidney. Ectopic expression of miR-192/215 increased E-cadherin levels via repressed translation of ZEB2 mRNA, in the presence and absence of TGF-β, as demonstrated by a ZEB2 3′-untranslated region luciferase reporter assay. However, ectopic expression of miR-192/215 did not affect the expression of matrix proteins or their induction by TGF-β. In contrast, CTGF increased miR-192/215 levels, causing a decrease in ZEB2, and consequently increased E-cadherin mRNA.CONCLUSIONSThese data demonstrate the linking role of miRNA-192/215 and ZEB2 in TGF-β/CTGF–mediated changes in E-cadherin expression. These changes appear to occur independently of augmentation of matrix protein synthesis, suggesting that a multistep EMT program is not necessary for fibrogenesis to occur.

Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer

MicroRNAs are small, non-coding RNAs that influence gene regulatory networks by post-transcriptional regulation of specific messenger RNA targets. MicroRNA expression is dysregulated in human malignancies, frequently leading to loss of expression of certain microRNAs. We report that expression of hsa-miR-342, a microRNA encoded in an intron of the gene EVL, is commonly suppressed in human colorectal cancer. The expression of hsa-miR-342 is coordinated with that of EVL and our results indicate that the mechanism of silencing is CpG island methylation upstream of EVL. We found methylation at the EVL/hsa-miR-342 locus in 86% of colorectal adenocarcinomas and in 67% of adenomas, indicating that it is an early event in colorectal carcinogenesis. In addition, we observed a higher frequency of methylation (56%) in histologically normal colorectal mucosa from individuals with concurrent cancer compared to mucosa from individuals without colorectal cancer (12%), suggesting the existence of a 'field defect' involving methylated EVL/hsa-miR-342. Furthermore, reconstitution of hsa-miR-342 in the colorectal cancer cell line HT-29 induced apoptosis, suggesting that this microRNA could function as a proapoptotic tumor suppressor. In aggregate, these results support a novel mechanism for silencing intronic microRNAs in cancer by epigenetic alterations of cognate host genes.

Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients

IntroductionMicroRNAs are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their targeted mRNAs. It is known that aberrant microRNA expression can play important roles in cancer, but the role of microRNAs in autoimmune diseases is only beginning to emerge. In this study, the expression of selected microRNAs is examined in rheumatoid arthritis.MethodsTotal RNA was isolated from peripheral blood mononuclear cells obtained from patients with rheumatoid arthritis, and healthy and disease control individuals, and the expression of miR-146a, miR-155, miR-132, miR-16, and microRNA let-7a was analyzed using quantitative real-time PCR.ResultsRheumatoid arthritis peripheral blood mononuclear cells exhibited between 1.8-fold and 2.6-fold increases in miR-146a, miR-155, miR-132, and miR-16 expression, whereas let-7a expression was not significantly different compared with healthy control individuals. In addition, two targets of miR-146a, namely tumor necrosis factor receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK-1), were similarly expressed between rheumatoid arthritis patients and control individuals, despite increased expression of miR-146a in patients with rheumatoid arthritis. Repression of TRAF6 and/or IRAK-1 in THP-1 cells resulted in up to an 86% reduction in tumor necrosis factor-α production, implicating that normal miR-146a function is critical for the regulation of tumor necrosis factor-α production.ConclusionsRecent studies have shown that synovial tissue and synovial fibroblasts from patients with rheumatoid arthritis exhibit increased expression of certain microRNAs. Our data thus demonstrate that microRNA expression in rheumatoid arthritis peripheral blood mononuclear cells mimics that of synovial tissue/fibroblasts. The increased microRNA expression in rheumatoid arthritis patients is potentially useful as a marker for disease diagnosis, progression, or treatment efficacy, but this will require confirmation using a large and well defined cohort. Our data also suggest a possible mechanism contributing to rheumatoid arthritis pathogenesis, whereby miR-146a expression is increased but unable to properly function, leading to prolonged tumor necrosis factor-α production in patients with rheumatoid arthritis.