miR-148 targets human DNMT3b protein coding region

Duursma, Anja; Kedde, Martijn; Schrier, Mariëtte; Sage, Carlos le; Agami, Reuven

doi:10.1261/rna.972008

Cited by 525 publications

(376 citation statements)

References 33 publications

(44 reference statements)

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“…This suggests that miR-148a may not directly target RUNX3. Previous studies have already confirmed that miR-148a could modulate DNMT1 and DNMT3B protein expression (Braconi et al, 2010;Duursma et al, 2008;Pan et al, 2010;Zhu et al, 2012). Therefore, our results show that overexpression of miR148a in gastric cancer cells might upregulate RUNX3 expression through the modulation of DNMTs.…”

Section: Overexpression Of Mir-148a Downregulated Runx3 Gene Expressionsupporting

confidence: 79%

MicroRNA-148a Can Regulate Runt-Related Transcription Factor 3 Gene Expression via Modulation of DNA Methyltransferase 1 in Gastric Cancer

Zuo

Xia

et al. 2013

Molecules and Cells

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Underexpression of the gene runt-related transcription factor 3 (RUNX3), an important tumor suppressor, is known to contribute to gastric cancer progression. However, the mechanism underlying aberrant RUNX3 expression has not been fully elucidated. We investigated the role of microRNA-148a (miR-148a) and DNA methyltransferases (DNMTs) in RUNX3 promoter methylation and gene expression. RUNX3 mRNA, RUNX3 protein, and methylation levels were assayed in human gastric cancer tissues and matched normal tissues, and AGS and BGC-823 cells by real-time reverse transcription PCR, Western blot, and methylation-specific PCR, respectively. A correlation between RUNX3 mRNA levels and that of miR-148a was also investigated in gastric cancer tissues. We found that RUNX3 mRNA levels were significantly downregulated in gastric cancer tissues compared with their matched normal tissues, and were closely associated with miR-148a expression. After treatment of human gastric cancer AGS and BGC-823 cells with the DNA methylation inhibitor 5-aza-2'-deoxycytidine, a significant increase in RUNX3 mRNA, RUNX3 protein, and the non-methylated form of the RUNX3 promoter were observed relative to untreated cells. Enforced expression of miR-148a, which can modulate DNMT1 and DNMT3B, also increased the expression of RUNX3 in gastric cancer cells. Knockdown of DNMT1 was associated with increased levels of RUNX3 mRNA and RUNX3 protein, while knockdown of DNMT3B did not have any effect on these in BGC-823 cells. Our results show that miR-148a may regulate RUNX3 expression through modulation of DNMT1-dependent DNA methylation in gastric cancer and highlight a miRNA-epigenetics regulation mechanism of gene expression.

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Section: Overexpression Of Mir-148a Downregulated Runx3 Gene Expressionsupporting

confidence: 79%

MicroRNA-148a Can Regulate Runt-Related Transcription Factor 3 Gene Expression via Modulation of DNA Methyltransferase 1 in Gastric Cancer

Zuo

Xia

et al. 2013

Molecules and Cells

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“…This is in consistence with the most recent work demonstrating that miRNAs can interact with the coding region of mRNA 45,46 . For example, miR-148 represses DNA methyltransferase 3b gene expression through a region in its coding sequence 47 . Strikingly, we found that the binding sites of miR-484 in the amino acid coding sequences of Fis1 are evolutionarily conserved in many species, including human, rat and mouse.…”

Section: Discussionmentioning

confidence: 99%

miR-484 regulates mitochondrial network through targeting Fis1

et al. 2012

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mitochondria constantly undergo fusion and fission, two necessary processes for the maintenance of organelle fidelity. The abnormal mitochondrial fission participates in the pathogenesis of many diseases, but its regulation remains poorly understood. Here we show that miR-484 can suppress translation of mitochondrial fission protein Fis1, and inhibit Fis1-mediated fission and apoptosis in cardiomyocytes and in the adrenocortical cancer cells. We demonstrate that Fis1 is necessary for mitochondrial fission and apoptosis, and is upregulated during anoxia, whereas miR-484 is downregulated. miR-484 is able to attenuate Fis1 upregulation and mitochondrial fission, by binding to the amino acid coding sequence of Fis1 and inhibiting its translation. In exploring the underlying mechanism of miR-484 downregulation upon apoptosis, we observe that Foxo3a transactivates miR-484 expression. Foxo3a transgenic or knockout mice exhibit, respectively, a high or low level of miR-484 and a reduced or enhanced mitochondrial fission, apoptosis and myocardial infarction. our data reveal a model of mitochondrial fission regulation by a microRnA.

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“…Target sites of animal and human mRNAs are usually at the 3'-untranslated region (UTR), although there are examples of target sites in the coding region as well (Duursma et al, 2008).…”

Section: Biogenesis Of Mirnas and Gene Regulation By Mirnasmentioning

confidence: 99%

MicroRNAs from biology to future pharmacotherapy: Regulation of cytochrome P450s and nuclear receptors

Nakajima

Yokoi

2011

Pharmacology & Therapeutics

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MicroRNAs (miRNAs) are a family of short, non-coding RNA whose final product is a 22-nucleotide functional RNA molecule. They regulate the expression of target genes by binding to complementary regions of transcripts to repress their translation or promote mRNA degradation. Since miRNAs regulate every aspect of cellular function, their dysregulation is associated with a variety of diseases including cancer, diabetes, and cardiovascular diseases.Therefore, miRNAs are now considered new therapeutic targets. However, the roles of miRNAs in the metabolism of xenobiotics and endobiotics have only recently been revealed.This review describes the current knowledge on the regulation of cytochrome P450s and nuclear receptors by miRNAs, the physiological and clinical significance. The miRNA expression is readily altered by chemicals, carcinogens, drugs, hormones, stress, or diseases, and the dysregulation of specific miRNAs might lead to changes in the drug metabolism potency or pharmacokinetics as well as pathophysiological changes. In the field of pharmacogenomics, the evaluation of miRNA-related polymorphisms would provide useful information for personalized medicine. Utilizing miRNAs opens a new era in the fields of drug metabolism and pharmacokinetics as well as toxicology.

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miR-148 targets human DNMT3b protein coding region

Cited by 525 publications

References 33 publications

MicroRNA-148a Can Regulate Runt-Related Transcription Factor 3 Gene Expression via Modulation of DNA Methyltransferase 1 in Gastric Cancer

MicroRNA-148a Can Regulate Runt-Related Transcription Factor 3 Gene Expression via Modulation of DNA Methyltransferase 1 in Gastric Cancer

miR-484 regulates mitochondrial network through targeting Fis1

MicroRNAs from biology to future pharmacotherapy: Regulation of cytochrome P450s and nuclear receptors

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