Recently microRNAs (miRNAs) have been recognized as powerful regulators of many genes and pathways involved in the pathogenesis of inflammatory diseases including Systemic Lupus Erythematosus (SLE). SLE is an autoimmune disease characterized by production of various autoantibodies, inflammatory immune cells, and dysregulation of epigenetic changes. Several candidate miRNAs regulating inflammation and autoimmunity in SLE are described. In this study, we found significant increases in the expression of miR21, miR25, and miR186 in peripheral blood mononuclear cells (PBMCs) of SLE patients compared to healthy controls. However, miR146a was significantly decreased in SLE patients compared to healthy controls and was negatively correlated with plasma estradiol levels and with SLE disease activity scores (SLEDAI). We also found that protein levels of IL-12 and IL-21 were significantly increased in SLE patients as compared to healthy controls. Further, our data shows that protein levels of IL-12 were positively correlated with miR21 expression and protein levels of IL-21 positively correlated with miR25 and miR186 expression in SLE patients. In addition, we found that levels of miR21, miR25, and miR186 positively correlated with SLEDAI and miR146a was negatively correlated in SLE patients. Thus, our data shows a dynamic interplay between disease pathogenesis and miRNA expression. This study has translational potential and may identify novel therapeutic targets in patients with SLE.

• cytokines/chemokines
• estradiol
• inflammation
• microRNAs
• systemic lupus erythematosus

• Animals
• Biomarkers
• Biomarkers, Tumor
• Cell Transformation, Neoplastic/genetics
• Cell Transformation, Neoplastic/metabolism
• Cytokines/metabolism
• DNA Damage
• Disease Progression
• Disease Susceptibility
• Gene Expression Regulation
• Humans
• Inflammasomes/metabolism
• Inflammation/complications
• Inflammation/genetics
• Inflammation/metabolism
• Inflammation Mediators/metabolism
• Neoplasms/etiology
• Neoplasms/metabolism
• Neoplasms/pathology
• Oxidative Stress
• Signal Transduction

• Firmicutes
• corn
• dietary miRNAs
• gut microbiota
• plant

• U.S. Department of Agriculture
• Office of Dietary Supplements

• feces
• hepatocellular carcinoma
• intestinal microRNAs
• quantitative real-time PCR assays
• reference genes

• diabetic retinopathy
• inflammation pathway
• miRNAs

• meta-analysis
• polymorphisms
• ulcerative colitis

• Colitis, Ulcerative/genetics
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Male
• MicroRNAs/genetics
• Polymorphism, Single Nucleotide

• Polycystic ovary syndrome
• antiandrogenic therapy
• biomarker
• mir-155
• visceral adipose index

• Androgen Antagonists/therapeutic use
• Biomarkers/blood
• Female
• Humans
• MicroRNAs/blood
• Polycystic Ovary Syndrome/blood
• Polycystic Ovary Syndrome/drug therapy

The current study seeks to resolve the discrepancy in the literature regarding the cross-kingdom transfer of plant microRNAs (miRNAs) into mammals using an improved miRNA processing and detection method. Two studies utilizing C57BL/6 mice were performed. In the first study, mice were fed an AIN-93M diet and gavaged with water, random deoxynucleotide triphosphates (dNTP) or isolated corn miRNAs for two weeks (n = 10 per group). In the second study, mice were fed an AIN-93M diet, or the diet supplemented with 3% fresh or autoclaved corn powder for two weeks (n = 10 per group). Corn miRNA levels were analyzed in blood and tissue samples by real-time PCR (RT-PCR) following periodate oxidation and β elimination treatments to eliminate artifacts. After removing false positive detections, there were no differences in corn miRNA levels between control and treated groups in cecal, fecal, liver and blood samples. Using an in vitro digestion system, corn miRNAs in AIN-93M diet or in the extracts were found to be extensively degraded. Less than 1% was recovered in the gastrointestinal tract after oral and gastric phases. In conclusion, no evidence of increased levels of corn miRNAs in whole blood or tissues after supplementation of corn miRNAs in the diet was observed in a mouse model.

• C57BL/6 mouse
• corn
• cross-kingdom transfer
• miRNA
• periodate oxidation

• Administration, Oral
• Animal Feed
• Animals
• Biological Availability
• Cecum/metabolism
• Feces/chemistry
• Gastrointestinal Absorption
• Liver/metabolism
• Male
• Mice, Inbred C57BL
• MicroRNAs/blood
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA Stability
• RNA, Plant/blood
• RNA, Plant/genetics
• RNA, Plant/metabolism
• Time Factors
• Tissue Distribution
• Zea mays/genetics

To investigate the miRNA expression in colonic mucosal biopsies from endoscopically inflamed and non inflamed regions of ulcerative colitis (UC) patients.

Colonic mucosal pinch biopsies were analyzed from the inflamed and non inflamed regions of same UC patient. Total RNA was isolated and differential miRNA profiling was done using microarray platform. Quantitative Real Time PCR was performed in colonic biopsies from inflamed (n = 8) and non-inflamed (n = 8) regions of UC and controls (n = 8) to validate the differential expression of miRNA. Potential targets of dysregulated miRNA were identified by using in silico prediction tools and probable role of these miRNA in inflammatory pathways were predicted.

The miRNA profile of inflamed colonic mucosa differs significantly from the non-inflamed. Real time PCR analysis showed that some of the miRNA were differentially expressed in the inflamed mucosa as compared to non inflamed mucosa and controls (miR-125b, miR-223, miR-138, and miR-155), while (miR-200a) did not show any significant changes. In contrast to microarray, where miR-378d showed downregulation in the inflamed mucosa, qRT-PCR showed a significant upregulation in the inflamed mucosa as compared to the non inflamed. The in silico prediction analysis revealed that the genes targeted by these miRNAs play role in the major signaling pathways like MAPK pathway, NF-κB signaling pathway, cell adhesion molecules which are all assciated with UC.

The present study reports disease specific alteration in the expression of miR-125b, miR-155, miR-223 and miR-138 in UC patients and also predict their biological significance.

• Ulcerative colitis
• Colon mucosa
• MicroRNA
• Microarray
• qRT-PCR
• In silico analysis

• Adult
• Biopsy
• Cell Adhesion Molecules/metabolism
• Colitis, Ulcerative/diagnostic imaging
• Colitis, Ulcerative/genetics
• Colitis, Ulcerative/pathology
• Colon/diagnostic imaging
• Colon/pathology
• Colonoscopy
• Computer Simulation
• Down-Regulation
• Female
• Gene Expression Profiling
• Humans
• Intestinal Mucosa/pathology
• MAP Kinase Signaling System/genetics
• Male
• MicroRNAs/metabolism
• Microarray Analysis
• Middle Aged
• NF-kappa B/metabolism
• Real-Time Polymerase Chain Reaction
• Up-Regulation

• Animals
• Male
• Mass Spectrometry
• Mice
• Mice, Inbred C57BL
• MicroRNAs/metabolism
• Periodic Acid/chemistry
• RNA, Plant/metabolism

• U.S. Department of Agriculture
• Office of Dietary Supplements

MicroRNAs are small non-coding RNAs that play an important role in regulating the gene expression of their target genes. SNP miR-196a-2 rs11614913 and miR-499 rs3746444 are reported to have association with the risk and prognosis of multiple-types of inflammatory diseases including IBD. This study was conducted to show if any association of SNP miR-196a-2rs11614913 and miR-499 rs3746444 exists with ulcerative colitis (UC) patients of north Indian population and how these polymorphisms modulate the expression profile of the respective miRNAs.

A total of 638 participants including 197 UC patients and 441 controls were included in this study. Polymorphisms were genotyped by PCR-RFLP and the miRNA expression was measured using qRT-PCR. Genotypes and allele frequencies were calculated using SPSS 16 software.

MiR-196a-2 rs11614913 (C>T) and miR-499 rs3746444 (T>C) were found to be associated with UC. TT genotype of miR-196a-2 rs11614913 (p = 0.03) was negatively associated with UC whereas the heterozygous TC genotype of miR-499 rs3746444 (p = 0.003) was showing positive association with UC. Patients having a combination of both SNPs, developed disease at older age and they suffered from severe disease extent. Genotype that showed association with the disease also showed correlation with the changes in miRNA expression.

In this study we found miR-196a-2 rs11614913 and miR-499 rs3746444 were associated with UC in north Indian population. We found the genotype that showed association with UC also altered the expression of respective miRNA in the patient harboring the genotype. There was correlation between associated genotype and altered miRNA expression.

• gastric adenocarcinoma
• microrna expression profile
• epstein-barr virus
• formalin fixed tissue
• plasma
• biomarker
• honduras

• Adenocarcinoma/genetics
• Adenocarcinoma/metabolism
• Adenocarcinoma/virology
• Aged
• Aged, 80 and over
• Case-Control Studies
• Epstein-Barr Virus Infections/genetics
• Epstein-Barr Virus Infections/metabolism
• Epstein-Barr Virus Infections/virology
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Herpesvirus 4, Human/genetics
• Herpesvirus 4, Human/isolation & purification
• Humans
• Male
• MicroRNAs/blood
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Middle Aged
• Pilot Projects
• RNA, Neoplasm/blood
• RNA, Neoplasm/genetics
• RNA, Neoplasm/metabolism
• RNA, Viral/blood
• RNA, Viral/genetics
• RNA, Viral/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/virology

• U10 CA181009 NCI NIH HHS
• KL2 TR001109 NCATS NIH HHS
• P30 CA016086 NCI NIH HHS
• HHSN261200800001C NCI NIH HHS
• P30 CA068485 NCI NIH HHS
• HHSN261200800001E NCI NIH HHS
• K07 CA125588 NCI NIH HHS
• R21 CA155543 NCI NIH HHS

Helicobacter pylori cause chronic inflammation favouring gastric carcinogenesis, and its eradication may prevent malignant transformation. We evaluated whether H. pylori infection and its eradication modify the expression of inflammatory mediators in patients with chronic gastritis. Furthermore, we assessed whether microRNAs modulate inflammatory pathways induced by H. pylori and identified miRNA–gene interaction networks. mRNA and protein expression of TNFA, IL6, IL1B, IL12A, IL2 and TGFBRII and miRNAs miR‐103a‐3p, miR‐181c‐5p, miR‐370‐3p, miR‐375 and miR‐223‐3p were evaluated in tissue samples from 20 patients with chronic gastritis H. pylori negative (Hp−) and 31 H. pylori positive (Hp+), before and three months after bacterium eradication therapy, in comparison with a pool of Hp− normal gastric mucosa. Our results showed that H. pylori infection leads to up‐regulation of TNFA, IL6, IL12A and IL2 and down‐regulation of miRNAs. Bacterium eradication reduces the expression of TNFA and IL6 and up‐regulates TGFBRII and all investigated miRNAs, except miR‐223‐3p. Moreover, transcriptional profiles of inflammatory mediators and miRNAs after eradication are different from the non‐infected group. Deregulated miRNA–mRNA interaction networks were observed in the Hp+ group before and after eradication. Therefore, miRNAs modulated cytokine expression in the presence of H. pylori and after its eradication, suggesting that miRNAs participate in the pathological process triggered by H. pylori in the gastric mucosa.

Emerging evidence has implicated microRNAs in regulating the production of multiple inflammatory mediators including cytokines and chemokines. We previously elucidated the dynamic activation of key signals that link colitis to colorectal cancer. In this study, we observed a sharp increase in the levels of matrix metalloproteinases (Mmps) that provided a basis for the inflammation-cancer link, and we questioned whether this was a consequence of the dysregulation of Mmp-specific microRNAs, at least partly. We assayed a panel of murine microRNAs that were predicted to target Mmps and found they were downregulated in the inflammation-cancer link. Furthermore, we demonstrated that three murine microRNAs, namely miR-128, -134, and -330, can target the three Mmps Mmp3, Mmp10, and Mmp13, respectively. We also found that the level of the microRNA-processing enzyme Dicer1 was decreased in the inflammation-cancer link. These microRNAs functioned as tumor suppressors in colon cancer cells, attenuating the proliferation, migration, and invasion potential of murine colon cancer cells as well as angiogenesis and the growth of tumors derived from these cells. Our results suggest that microRNAs modulate the production of key inflammatory mediators and that microRNA dysfunction may contribute to the non-resolving inflammation associated with cancer.

• Dicer1
• colitis-associated cancer
• matrix metalloproteinases
• microRNAs
• non-resolving inflammation

• EMT
• MET
• cancer
• microRNAs
• transcription factor

Ulcerative Colitis (UC) is a type of inflammatory bowel disease, considered as an important disease of gastrointestinal tract having a huge impact on the health of the patient. Prolonged inflammation of colon in UC patients increases the risk of developing colorectal cancer. MiRNA are reported as a connecting link between inflammation and cancer. Differential miRNA expression is reported in Crohn’s disease (CD) patients involving various regions of the gastrointestinal tract. The current study was performed to dissect out the site specific miRNA expression in the colon biopsy samples of UC patients from Northern India.

Biopsy samples were collected from UC patients and healthy controls from Rectosigmoid Area (RS) and Ascending Colon (AC). MiRNA expression was compared between patients with RS and AC using a microarray platform. Differential expression was further validated by Real Time PCR analysis. Demographic and pathological data of UC -associated CRC patients was collected from the hospital database and analyzed for assessing the site of cancer.

Upon analysis of data generated on a microarray platform and qRT PCR revealed that the expression of six miRNAs hsa-miR-146b-5p, hsa-miR-335-3p, hsa-miR-342-3p, hsa-miR-644b-3p, hsa-miR-491-3p, hsa-miR-4732-3p were downregulated in patients where RS was involved as compared to AC. The expression of hsa-miR-141-3p was upregulated in patients where RS region was involved as compared to AC. Analysis of the registered UC patient’s database from the hospital revealed that the site of CRC was predomimnantly the rectosigmoid region of the colon in most of the cases.

This is the first study to show the differential expression of miRNA involving different sites of colon in UC patients. Taking our data and previous reports into consideration, we propose that differential miRNA expression during UC perhaps contribute in the development of UC-associated CRC at the rectosigmoid area.

• atherosclerosis
• biomarkers
• cardiovascular disease
• microRNA

MicroRNAs (miRNAs) are noncoding regulatory sequences that govern posttranscriptional inhibition of genes through binding mainly at regulatory regions. The regulatory mechanism of miRNAs are influenced by complex crosstalk among single nucleotide polymorphisms (SNPs) within miRNA seed region and epigenetic modifications. Circulating miRNAs exhibit potential characteristics as stable biomarker. Functionally, miRNAs are involved in basic regulatory mechanisms of cells including inflammation. Thus, miRNA dysregulation, resulting in aberrant expression of a gene, is suggested to play an important role in disease susceptibility. This review focuses on the role of miRNA as diagnostic marker in pathogenesis of lung inflammatory diseases and in cardiac remodelling events during inflammation. From recent reports, In this context, the information about the models in which miRNAs expression were investigated including types of biological samples, as well as on the methods for miRNA validation and prediction/definition of their gene targets are emphasized in the review. Besides disease pathogenesis, promising role of miRNAs in early disease diagnosis and prognostication is also discussed. However, some miRNAs are also indicated with protective role. Thus, identifications and usage of such potential miRNAs as well as disruption of disease susceptible miRNAs using antagonists, antagomirs, are imperative and may provide a novel therapeutic approach towards combating the disease progression.

• Biomarkers/metabolism
• Gene Ontology
• Gene Regulatory Networks
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Protein Interaction Maps/genetics
• ROC Curve
• Sepsis/diagnosis
• Sepsis/genetics
• Signal Transduction/genetics

• Alveolar Epithelial Cells/drug effects
• Alveolar Epithelial Cells/metabolism
• Alveolar Epithelial Cells/pathology
• Anti-Inflammatory Agents, Non-Steroidal/pharmacology
• Cell Line
• Diterpenes/pharmacology
• Drugs, Chinese Herbal/pharmacology
• Gene Silencing
• Glutathione/metabolism
• Humans
• I-kappa B Proteins/metabolism
• Interleukin-6/biosynthesis
• Interleukin-8/biosynthesis
• MicroRNAs/antagonists & inhibitors
• MicroRNAs/biosynthesis
• MicroRNAs/genetics
• NF-KappaB Inhibitor alpha
• NF-kappa B/antagonists & inhibitors
• Oxidative Stress/drug effects
• Smoke/adverse effects
• Nicotiana/adverse effects

MicroRNAs (miRNAs) function to modulate gene expression, and through this property they regulate a broad spectrum of cellular processes. They can circulate in blood and thereby mediate cell-to-cell communication. Aging involves changes in many cellular processes that are potentially regulated by miRNAs, and some evidence has implicated circulating miRNAs in the aging process. In order to initiate a comprehensive assessment of the role of circulating miRNAs in aging, we have used deep sequencing to characterize circulating miRNAs in the serum of young mice, old mice, and old mice maintained on calorie restriction (CR). Deep sequencing identifies a set of novel miRNAs, and also accurately measures all known miRNAs present in serum. This analysis demonstrates that the levels of many miRNAs circulating in the mouse are increased with age, and that the increases can be antagonized by CR. The genes targeted by this set of age-modulated miRNAs are predicted to regulate biological processes directly relevant to the manifestations of aging including metabolic changes, and the miRNAs themselves have been linked to diseases associated with old age. This finding implicates circulating miRNAs in the aging process, raising questions about their tissues of origin, their cellular targets, and their functional role in metabolic changes that occur with aging.