MicroRNA-22 and microRNA-140 suppress NF-κB activity by regulating the expression of NF-κB coactivators.
ABSTRACT Nuclear factor κB (NF-κB) is a transcription factor that regulates a set of genes that are critical to many biological phenomena, including liver tumorigenesis. To identify microRNAs (miRNAs) that regulate NF-κB activity in the liver, we screened 60 miRNAs expressed in hepatocytes for their ability to modulate NF-κB activity. We found that miRNA-22 and miRNA-140-3p significantly suppressed NF-κB activity by regulating the expression of nuclear receptor coactivator 1 (NCOA1) and nuclear receptor-interacting protein 1 (NRIP1), both of which are NF-κB coactivators. Our results provide new information about the roles of miRNAs in the regulation of NF-κB activity.
- SourceAvailable from: Luca Agnelli[Show abstract] [Hide abstract]
ABSTRACT: PURPOSE: Primary plasma cell leukemia (pPCL) is a rare and very aggressive form of plasma cell dyscrasia. To date, no information on miRNA expression in pPCL has been reported. This study was aimed at investigating the involvement of miRNAs in pPCL and their possible relationship with higher tumor aggressiveness. Experimental design: Global miRNA expression profiles were analyzed in highly-purified malignant plasma cells from 18 pPCL untreated patients included in a prospective clinical trial. MiRNA expression patterns were evaluated in comparison with a representative series of multiple myeloma (MM) patients, in relation to the most recurrent chromosomal abnormalities (as assessed by fluorescence in situ hybridization and single nucleotide polymorphism-array analysis), and in association with clinical outcome. MiRNA expression was also integrated with gene expression profiles in pPCL and MM samples. RESULTS: We identified a series of deregulated miRNAs in pPCL (42 up- and 41 down-regulated) in comparison with MM. Some of them, based on their reported functions and putative target genes computed by integrative analysis, might have a role in the pathobiology of pPCL. As regards to chromosomal aberrations, the expression of some miRNAs mapped to hot-spot altered regions was associated with DNA copy number of the corresponding loci. Finally, four miRNA (miR-497, miR-106b, miR-181a* and miR-181b) were identified having expression levels correlated with treatment response, and four (miR-92a, miR-330-3p, miR-22, and miR-146a) with clinical outcome. CONCLUSIONS: Overall, our study provides insights into the possible contribution of miRNAs in the pathogenesis of pPCL and suggests targets for future therapeutic investigations.Clinical Cancer Research 04/2013; · 7.84 Impact Factor
Article: miRNAs and estrogen action.[Show abstract] [Hide abstract]
ABSTRACT: MicroRNAs (miRNAs) are short, noncoding RNAs that generally base-pair within the 3' untranslated region of target mRNAs causing translational inhibition and/or mRNA degradation. Estradiol (E(2)) and other estrogen receptor (ER) ligands suppress or stimulate miRNA expression in human breast cancer cells, endometrial cells, rat mammary gland, and mouse uterus, and post-translationally regulate protein expression. Aberrant miRNA expression is implicated in estrogen-related breast and endometrial cancers, and several miRNAs downregulate ERα. The role of estrogen-regulated miRNA expression, the target genes of these miRNAs, and the role of miRNAs in health and disease is a 'hot' area of research that will yield new insight into molecular mechanisms of estrogen action.Trends in Endocrinology and Metabolism 04/2012; 23(5):223-33. · 8.90 Impact Factor
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ABSTRACT: Hepatocellular carcinoma (HCC) is a threat to public health worldwide. We previously identified the association of a single nucleotide polymorphism (SNP) at the promoter region of the MHC class I polypeptide-related sequence A (MICA) gene with the risk of hepatitis-virus-related HCC. Because this SNP affects MICA expression levels, regulating MICA expression levels may be important in the prevention of HCC. We herein show that the microRNA (miR) 25-93-106b cluster can modulate MICA levels in HCC cells. Overexpression of the miR 25-93-106b cluster significantly suppressed MICA expression. Conversely, silencing of this miR cluster enhanced MICA expression in cells that express substantial amounts of MICA. The changes in MICA expression levels by the miR25-93-106b cluster were biologically significant in an NKG2D-binding assay and an in vivo cell-killing model. These data suggest that the modulation of MICA expression levels by miRNAs may be a useful method to regulate HCCs during hepatitis viral infection.Scientific Reports 09/2013; 3:2739. · 5.08 Impact Factor