Flavonoids inhibit the AU-rich element binding of HuC

Kwak, Ho Young; Jeong, Kyung‐Chae; Chae, Min-Ju; Kim, Soo-Youl; Park, Woong-Yang

doi:10.5483/bmbrep.2009.42.1.041

Cited by 15 publications

(13 citation statements)

References 23 publications

(26 reference statements)

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“…The 3’-untranslated regions (3’-UTR) of BRF1 and BRF2 mRNAs are AU-rich, which may influence their stability [ 42 ]. Various classes of polyphenols have been shown to post-transcriptionally regulate levels of mRNA containing AU-rich elements by raising expression of RNA binding proteins [ 46 – 49 ]. To test if daidzein stabilizes BRF mRNAs, as a potential mechanism of induction, we treated MCF-7 cells with the transcription inhibitor actinomycin D [ 41 ] and monitored mRNA decay using qRT-PCR.…”

Section: Resultsmentioning

confidence: 99%

Induction of proto-oncogene BRF2 in breast cancer cells by the dietary soybean isoflavone daidzein

et al. 2015

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BackgroundBRF2 is a transcription factor required for synthesis of a small group of non-coding RNAs by RNA polymerase III. Overexpression of BRF2 can transform human mammary epithelial cells. In both breast and lung cancers, the BRF2 gene is amplified and overexpressed and may serve as an oncogenic driver. Furthermore, elevated BRF2 can be independently prognostic of unfavorable survival. Dietary soy isoflavones increase metastasis to lungs in a model of breast cancer and a recent study reported significantly increased cell proliferation in breast cancer patients who used soy supplementation. The soy isoflavone daidzein is a major food-derived phytoestrogen that is structurally similar to estrogen. The putative estrogenic effect of soy raises concern that high consumption of soy foods by breast cancer patients may increase tumor growth.MethodsExpression of BRF2 RNA and protein was assayed in ER-positive or –negative human breast cancer cells after exposure to daidzein. We also measured mRNA stability, promoter methylation and response to the demethylating agent 5-azacytidine. In addition, expression was compared between mice fed diets enriched or deprived of isoflavones.ResultsWe demonstrate that the soy isoflavone daidzein specifically stimulates expression of BRF2 in ER-positive breast cancer cells, as well as the related factor BRF1. Induction is accompanied by increased levels of non-coding RNAs that are regulated by BRF2 and BRF1. Daidzein treatment stabilizes BRF2 and BRF1 mRNAs and selectively decreases methylation of the BRF2 promoter. Functional significance of demethylation is supported by induction of BRF2 by the methyltransferase inhibitor 5-azacytidine. None of these effects are observed in an ER-negative breast cancer line, when tested in parallel with ER-positive breast cancer cells. In vivo relevance is suggested by the significantly elevated levels of BRF2 mRNA detected in female mice fed a high-isoflavone commercial diet. In striking contrast, BRF2 and BRF1 mRNA levels are suppressed in matched male mice fed the same isoflavone-enriched diet.ConclusionsThe BRF2 gene that is implicated in cancer can be induced in human breast cancer cells by the isoflavone daidzein, through promoter demethylation and/or mRNA stabilization. Dietary isoflavones may also induce BRF2 in female mice, whereas the converse occurs in males.

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Section: Resultsmentioning

confidence: 99%

Induction of proto-oncogene BRF2 in breast cancer cells by the dietary soybean isoflavone daidzein

et al. 2015

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“…However, the mechanism of action of these inhibitors in post-transcriptional regulation of inflammatory mediators has not been investigated. In a previous report, we described the interference of flavonoids with the interaction of the stabilizing factor HuC and the key inflammatory cytokine TNF-α (Kwak et al, 2009). In this study, we have verified the inhibitory effect of candidate chemicals for RNA-protein binding using EMSA and filter binding assay.…”

Section: Discussionmentioning

confidence: 69%

“…In a previous study, we demonstrated that flavonoids can inhibit the binding of HuC to the ARE of TNF-α mRNA (Kwak et al, 2009). For the present study, we screened chemicals for their ability to interfere with the interaction of HuR protein with TNF-α mRNA.…”

Section: Introductionmentioning

confidence: 99%

Chemical inhibitors destabilize HuR binding to the AU-rich element of TNF-α mRNA

et al. 2009

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Hu protein R (HuR) binds to the AU-rich element (ARE) in the 3'UTR to stabilize TNF-α mRNA. Here, we identified chemical inhibitors of the interaction between HuR and the ARE of TNF-α mRNA using RNA electrophoretic mobility gel shift assay (EMSA) and filter binding assay. Of 179 chemicals screened, we identified three with a half-maximal inhibitory concentration (IC 50 ) below 10 μM. The IC 50 of quercetin, b-40, and b-41 were 1.4, 0.38, and 6.21 μM, respectively, for binding of HuR protein to TNF-α mRNA. Quercetin and b-40 did not inhibit binding of tristetraprolin to the ARE of TNF-α mRNA. When LPS-treated RAW264.7 cells were treated with quercetin and b-40, we observed decreased stability of TNF-α mRNA and decreased levels of secreted TNF-α. From these results, we could find inhibitors for the TNF-α mRNA stability, which might be used advantageously for both the study for post-transcriptional regulation and the discovery of new anti-inflammation drugs.

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“…Total RNA was extracted from the cell lines using the TRIzol method according to the manufacturer's protocol [24]. Total RNA was reverse transcribed to cDNA using Superscript II reverse transcriptase (Invitrogen) and oligonucleotide primers.…”

Section: Methodsmentioning

confidence: 99%

Investigation of the interaction between the MIR-503 and CD40 genes in irradiated U937 cells

et al. 2012

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BackgroundMicroRNAs (miRNAs) are a group of small noncoding RNAs that take part in diverse biological processes by suppressing target gene expression. Relatively few miRNAs have been studied in detail, especially miR-503, and hence the biological relevance of majority remains to be uncovered. Whether altered expression of miRNA-503 affects the immunity response to radiotherapy has yet to be addressed.ResultsIn the present study, we applied ionizing radiation with a dose of either 0.1 Gy or 5 Gy to irradiate U937 cells to confirm CD40 as a miR-503 target, which was identified using a bioimformatics tool. In high dose (5 Gy) ionizing-irradiated U937 cells, expression of miR-503 was up regulated while the expression of CD40 gene was down regulated. Using the transfection of the miR-503 gene into U937 cells and Luciferase assay, we confirmed that miR-503 suppressed the expression of CD40, and was a negtive regulator of CD40.ConclusionsTo our knowledge, we are the first to describe involvement of miR-503 in radiobiological effect at a molecular level. This initial finding suggested the evidence that ionizing radiation could alter the expression of miR-503 and its target gene CD40, and may be very important to shed light on a possible mechanism regarding regulation of immune responses to irradiation.

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Flavonoids inhibit the AU-rich element binding of HuC

Cited by 15 publications

References 23 publications

Induction of proto-oncogene BRF2 in breast cancer cells by the dietary soybean isoflavone daidzein

Induction of proto-oncogene BRF2 in breast cancer cells by the dietary soybean isoflavone daidzein

Chemical inhibitors destabilize HuR binding to the AU-rich element of TNF-α mRNA

Investigation of the interaction between the MIR-503 and CD40 genes in irradiated U937 cells

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