• DNA methylation
• epigenetic diet
• histone modification
• microRNAs
• prediabetes

• DNA Methylation
• Epigenesis, Genetic
• Gene Expression Regulation/genetics
• Genetic Predisposition to Disease
• Histone Code/genetics
• Histones/genetics
• Humans
• Metabolic Syndrome/genetics
• Metabolic Syndrome/pathology
• MicroRNAs/genetics

• Antimycin A
• H9c2 cell
• I/R
• Plk2
• apoptosis
• heart
• miR-128

miR-410-3p acts as an oncogene or a tumor suppressor in some malignancies. However, its role in rheumatoid arthritis (RA) is unknown. The study was conducted to investigate the effect of miR-410-3p on the pathogenesis of RA. Real-time RT-PCR was used to determine the mRNA levels of miR-410-3p in synovial tissues and fibroblast-like synoviocytes (FLSs). An ELISA was performed to examine the production levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and matrix metalloproteinase (MMP)-9. Western blotting was conducted to determine the protein levels of IκB-α, p-IκBα, p65, and p-p65. Nuclear factor (NF)-κB activation and nuclear translocation assays were performed to confirm the activation of NF-κB. We found that the expression level of miR-410-3p was downregulated in synovial tissues and FLSs from RA. Overexpression of miR-410-3p significantly reduced the secretion of TNF-α, IL-1β, IL-6, and MMP-9 in human RA fibroblast-like synoviocytes (HFLS-RA); whereas miR-410-3p inhibition increased the expression levels of these cytokines. Furthermore, miR-410-3p suppresses the activation of NF-κB signaling pathway. Moreover, NF-κB inhibitor restored the elevation of TNF-α, IL-1β, IL-6, and MMP-9 induced by miR-410-3p inhibition. Our results demonstrate that miR-410-3p acts an inflammatory suppressor in the pathogenesis of RA by regulating the NF-κB signaling pathway. These data suggest a novel function of miR-410-3p and provide insight into the complex mechanisms involved in RA.

• NF-κB signaling
• cytokines
• fibroblast-like synoviocytes
• miR-410-3p
• rheumatoid arthritis

• Diabetes and complications
• Epigenetics
• MicroRNAs

• Animals
• DNA Methylation
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/genetics
• Epigenesis, Genetic/physiology
• Gene Expression Regulation
• Humans
• MicroRNAs/genetics
• Promoter Regions, Genetic

Emerging evidence indicates that dysregulation of microRNAs (miRNAs) contributes to hepatocellular carcinoma (HCC) tumorigenesis and development. Here, we found that miR-615-5p was obviously downregulated in HCC. Furthermore, the deficiency of demethylase KDM4B stimulated the CpG methylation of miR-615-5p promoter and then decreased the miR-615-5p expression. The Ras-related protein RAB24 was found to be downregulated by miR-615-5p. The low level of miR-615-5p increased the expression of RAB24 and facilitated HCC growth and metastasis in vitro and in vivo. Moreover, miR-615-5p suppresses HCC cell growth by influencing cell cycle progression and apoptosis. Downregulation of miR-615-5p and upregulation of RAB24 promotes the epithelial-mesenchymal transition (EMT), adhesion and vasculogenic mimicry (VM) of HCC cells, all of which contribute to cell motility and metastasis. Thus, miR-615-5p, who is downregulated by KDM4B-mediated hypermethylation in its promoter, functions as a tumor suppressor by inhibiting RAB24 expression in HCC. In conclusion, our findings characterize miR-615-5p as an important epigenetically silenced miRNA involved in the Rab-Ras pathway in hepatocellular carcinoma and expand our understanding of the molecular mechanism underlying hepatocarcinogenesis and metastasis.

• DNA methylation
• HCC
• gene regulation
• metastasis
• miRNAs

• endometrial cancer
• cimp
• methylation
• epimutation
• mir-663a
• dnmts
• miseq

• Adenomatous Polyposis Coli Protein/genetics
• Adult
• Aged
• Antigens, CD
• Biomarkers, Tumor/genetics
• Cadherins/genetics
• CpG Islands/genetics
• DNA Methylation/genetics
• Endometrial Neoplasms/genetics
• Endometrial Neoplasms/pathology
• Epigenesis, Genetic/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Genome, Human/genetics
• Humans
• MicroRNAs/genetics
• Middle Aged
• MutL Protein Homolog 1/genetics
• Mutation
• Promoter Regions, Genetic

FHL1 is an important tumor-suppressor that is downregulated in multiple tumors by unknown mechanisms. We demonstrated that miR-410 specifically targets the 3′UTR of FHL1. Furthermore, using DNA bisulfite modification and sequencing experiments, we demonstrated that the FHL1 promoter is hypermethylated in cancer cells. FHL1 methylation is increased upon miR-410 expression, suggesting that the regulation of FHL1 by miR-410 occurs by a dual mechanism. Using chromatin immunoprecipitation assays, we observed that miR-410 overexpression results in the increased binding of DNMT3A at the FHL1 promoter, which could explain how miR-410 regulates FHL1 methylation. Importantly, in vitro and in vivo results suggest that miR-410 may have oncogenic properties. Furthermore, both miR-410 and DNMT3A are upregulated in clinical human liver and colorectal tumors cancers. Our results suggest that miR-410 may function as an oncomiR and are consistent with its key function in regulating FHL1 in certain digestive system cancers.

The messenger RNA 3’-untranslated region (3’UTR) plays an important role in regulation of gene expression on the posttranscriptional level. The 3’UTR controls gene expression via orchestrated interaction between the structural components of mRNAs (cis-element) and the specific trans-acting factors (RNA binding proteins and non-coding RNAs). The crosstalk of these factors is based on the binding sequences and/or direct protein-protein interaction, or just functional interaction. Much new evidence that has accumulated supports the idea that several RNA binding factors can bind to common mRNA targets: to the non-overlapping binding sites or to common sites in a competitive fashion. Various factors capable of binding to the same RNA can cooperate or be antagonistic in their actions. The outcome of the collective function of all factors bound to the same mRNA 3’UTR depends on many circumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3’UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological conditions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these alterations and their impact on 3’UTR-directed posttranscriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer diagnostics and therapy based on 3’UTR binding factors and approaches to improve them.

• Translational control
• 3’-untranslated region
• MicroRNAs
• RNA binding proteins
• Cancer

• DNA methylation
• H-ras
• MiR-663
• epigenetics
• gene expression

Eukaryotic translation elongation factor 1A2 (eEF1A2) is a known proto-oncogene. We proposed that stimulation of the eEF1A2 expression in cancer tissues is caused by the loss of miRNA-mediated control.

Impact of miRNAs on eEF1A2 at the mRNA and protein levels was examined by qPCR and western blot, respectively. Dual-luciferase assay was applied to examine the influence of miRNAs on 3′-UTR of EEF1A2. To detect miRNA-binding sites, mutations into the 3′-UTR of EEF1A2 mRNA were introduced by the overlap extension PCR.

miR-663 and miR-744 inhibited the expression of luciferase gene attached to the 3′-UTR of EEF1A2 up to 20% and 50%, respectively. In MCF7 cells, overexpression of miR-663 and miR-744 reduced the EEF1A2 mRNA level by 30% and 50%. Analogous effects were also observed at the eEF1A2 protein level. In resveratrol-treated MCF7 cells the upregulation of mir-663 and mir-744 was accompanied by downregulation of EEF1A2 mRNA. Both miRNAs were able to inhibit the proliferation of MCF7 cells.

miR-663 and miR-744 mediate inhibition of the proto-oncogene eEF1A2 expression that results in retardation of the MCF7 cancer cells proliferation. Antitumour effect of resveratrol may include stimulation of the miR-663 and miR-744 expression.

• 3' Untranslated Regions/genetics
• Animals
• Antineoplastic Agents
• Base Sequence
• Binding Sites/genetics
• Brain Neoplasms/genetics
• Brain Neoplasms/pathology
• Cell Line, Tumor
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Glioma/genetics
• Glioma/pathology
• Humans
• Mice
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Molecular Sequence Data
• Neoplasm Invasiveness
• Proto-Oncogene Proteins c-akt/metabolism
• Proto-Oncogene Proteins c-met/genetics
• Proto-Oncogene Proteins c-met/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Signal Transduction/genetics