miR-21 Gene Expression Triggered by AP-1 Is Sustained through a Double-Negative Feedback Mechanism

Fujita, Shuji; Ito, Tsuyohito; Mizutani, Taketoshi; Minoguchi, Shigeru; Yamamichi, Nobutake; Sakurai, Kouhei; Iba, Hideo

doi:10.1016/j.jmb.2008.03.015

Cited by 381 publications

(432 citation statements)

References 47 publications

Supporting

Mentioning

404

Contrasting

Unclassified

Order By: Relevance

“…Recent reports indicate that miR-21 can be upregulated by two transcription factors, AP-1 and ETS1 (Fujita et al, 2008;Huang et al, 2009). This is consistent with our findings (Supplementary Figure 4) as both factors are known to be activated by the RAS/ ERK-signaling pathway (Karin, 1996;Paumelle et al, 2002).…”

Section: Discussionsupporting

confidence: 93%

Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs

et al. 2010

View full text Add to dashboard Cite

Cancer cells show characteristic gene expression profiles. Recent studies support the potential importance of micro-RNA (miRNA) expression signatures as biomarkers and therapeutic targets. The membrane-anchored protease regulator RECK is downregulated in many cancers, and forced expression of RECK in tumor cells results in decreased malignancy in animal models. RECK is also essential for mammalian development. In this study, we found that RECK is a target of at least three groups of miRNAs (miR-15b/16, miR-21 and miR-372/373); that RECK mutants lacking the target sites for these miRNA show augmented tumor/metastasis-suppressor activities; and that miR-372/373 are upregulated in response to hypoxia through HIF1a and TWIST1, whereas miR-21 is upregulated by RAS/ERK signaling. These data indicate that the hypoxia-and RAS-signaling pathways converge on RECK through miRNAs, cooperatively downregulating this tumor suppressor and thereby promoting malignant cell behavior.

show abstract

Section: Discussionsupporting

confidence: 93%

Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs

et al. 2010

View full text Add to dashboard Cite

show abstract

“…As previously reported (27), several conserved enhancer elements were found in the consensus sequence upstream of the transcription start site of the pri-miR-21 on the basis of TRANSFAC matrices, including Ets/PU.1, activator protein-1, serum response factor, CAAT/enhancer-binding protein-α, p53, and STAT3. 4 This suggests that highly conserved transcriptional regulatory mechanisms may operate on the pri-miR-21 promoter (Fig.…”

Section: Stat3 Negatively Regulates Mir-21 Transcriptionsupporting

confidence: 65%

The Modulation of MicroRNAs by Type I IFN through the Activation of Signal Transducers and Activators of Transcription 3 in Human Glioma

Ohno

Natsume

Kondo

et al. 2009

Molecular Cancer Research

View full text Add to dashboard Cite

Type I IFNs are involved in double-stranded RNA responses. Here, we investigated the possibility that IFN-β may induce or downregulate cellular microRNAs (miRNA) in human neoplasms and thereby use the RNA interference system to show antitumor effects. Because of its known connection to glioma biology, we focused on miR-21 among seven miRNAs influenced by IFN-β. We analyzed the effect of IFN-β treatment on miR-21 expression in glioma cells and intracranial glioma xenografts. IFN-β treatment reduced miR-21 expression in glioma cells markedly, and IFN-β administration suppressed the growth of glioma-initiating cell-derived intracranial tumors. The levels of primary miR-21 gene transcripts, precursor miR-21, and mature miR-21 decreased 6 hours after the addition of IFN-β, indicating that the reduction in miR-21 levels was due to transcriptional suppression. We did reporter assays to elucidate the IFN-β-mediated suppression of miR-21; the addition of signal transducers and activators of transcription 3 (STAT3)-expressing vectors induced the IFN-β-mediated suppression of miR-21, whereas STAT3-inhibiting agents inhibited the miR-21 suppression. Thus, the results of our study show that the downregulation of miR-21 contributes to the antitumor effects of IFN-β and that miR-21 expression is negatively regulated by STAT3 activation. These results highlight the importance of understanding the transcriptional regulation of the miRNAs involved in

show abstract

“…LPS increased the quantities of pri-miR-21, whereas LXA 4 abolished the LPS-induced pri-miR-21 expression (Figure 3a), consistent Because AP-1 is one of the conserved enhancer elements in the miR-21 promoter region, 41,42 we next explored whether AP-1 was involved in LPS-and/or LXA 4 -mediated miR-21 biosynthesis. Indeed, pretreatment of the A549 cells with the selective AP-1 inhibitor retinoid SR11302 43 reduced the production of LPS-induced miR-21, in a dose-and timedependent manner.…”

Section: Ap-1 Mediated Lps-induced Mir-21 Expressionsupporting

confidence: 57%

Lipoxin A4 activates alveolar epithelial sodium channel gamma via the microRNA-21/PTEN/AKT pathway in lipopolysaccharide-induced inflammatory lung injury

Cai

et al. 2015

Laboratory Investigation

View full text Add to dashboard Cite

Lipoxin A 4 (LXA 4 ), as an endogenously produced lipid mediator, promotes the resolution of inflammation. Previously, we demonstrated that LXA 4 stimulated alveolar fluid clearance through alveolar epithelial sodium channel gamma (ENaC-γ). In this study, we sought to investigate the mechanisms of LXA 4 in modulation of ENaC-γ in lipopolysaccharide (LPS)-induced inflammatory lung injury. miR-21 was upregulated during an LPS challenge and downregulated by LXA 4 administration in vivo and in vitro. Serum miR-21 concentration was also elevated in acute respiratory distress syndrome patients as compared with healthy volunteers. LPS increased miR-21 expression by activation of activator protein 1 (AP-1). In A549 cells, miR-21 upregulated phosphorylation of AKT activation via inhibition of phosphatase and tensin homolog (PTEN), and therefore reduced the expression of ENaC-γ. In contrast, LXA 4 reversed LPS-inhibited ENaC-γ expression through inhibition of AP-1 and activation of PTEN. In addition, an miR-21 inhibitor mimicked the effects of LXA 4 ; overexpression of miR-21 abolished the protective effects of LXA 4 . Finally, both AKT and ERK inhibitors (LY294002 and UO126) blocked effects of LPS on the depression of ENaC-γ. However, LXA 4 only inhibited LPS-induced phosphorylation of AKT. In summary, LXA 4 activates ENaC-γ in part via the miR-21/PTEN/AKT signaling pathway.

show abstract

miR-21 Gene Expression Triggered by AP-1 Is Sustained through a Double-Negative Feedback Mechanism

Cited by 381 publications

References 47 publications

Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs

Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs

The Modulation of MicroRNAs by Type I IFN through the Activation of Signal Transducers and Activators of Transcription 3 in Human Glioma

Lipoxin A4 activates alveolar epithelial sodium channel gamma via the microRNA-21/PTEN/AKT pathway in lipopolysaccharide-induced inflammatory lung injury

Contact Info

Product

Resources

About