MiR-34a inhibits lipopolysaccharide-induced inflammatory response through targeting Notch1 in murine macrophages

Jiang, Pei; Liu, Ronghua; Zheng, Yijie; Liu, Xiaoming; Chang, Lijun; Xiong, Sheng; Chu, Yiwei

doi:10.1016/j.yexcr.2012.03.018

Cited by 86 publications

(77 citation statements)

References 37 publications

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“…We then examined the effects of LPS activation of TNFα on levels of miR-34 in monocyte-derived macrophages from human donors. We were unable to confirm that miR-34a-5p is repressed by LPS as described previously (Jiang et al 2012). On the other hand, LPS treatment led to a strong attenuation of the miR-34a-3p strand.…”

Section: Discussioncontrasting

confidence: 71%

“…Mir-34a-5p decreased in all cases when normalized to miR-16 (Supplemental Table 2). However, the magnitude of the response was similar to that of the controls, and thus we were unsure that this was a bona fide effect, despite the previously published data obtained in the murine macrophage cell line (Jiang et al 2012). In contrast, LPS treatment reduced miR-34a-3p several-fold in four from five samples, leading overall to a significant effect using either miR-16 or miR-191 for normalization (Fig.…”

Section: Identification Of New Targets For Mir-34a-3pmentioning

confidence: 68%

“…Neither miRanda-mirSVR (Betel et al 2010) nor Targetscan (www.targetscan.org) showed a likely target site for miR-34a-5p in the TNFα UTR. However, miR-34a-5p reportedly regulates TNFα through NOTCH1 (Jiang et al 2012). We showed that NOTCH1 protein expression is attenuated in both HeLa cells and in LPS-stimulated macrophages by treatment with both 34a-5p and syn-pre-34a (Supplemental Fig.…”

Section: Identification Of New Targets For Mir-34a-3pmentioning

confidence: 80%

“…Increased TNFα derives from transcription as well as post-transcriptional regulation of its 3 ′ UTR (Raabe et al 1998). MiR-34 has been linked with the TNFα pathway previously (Jiang et al 2012). We hypothesized therefore that miR-34a-3p may also play a role in monocyte-derived macrophages, by suppressing TNFα levels directly.…”

Section: Identification Of New Targets For Mir-34a-3pmentioning

confidence: 98%

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Synthetic pre-microRNAs reveal dual-strand activity of miR-34a on TNF-α

Guennewig

Roos

Dogar

et al. 2013

RNA

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Functional microRNAs (miRNAs) are produced from both arms of their precursors (pre-miRNAs). Their abundances vary in contextdependent fashion spatiotemporarily and there is mounting evidence of regulatory interplay between them. Here, we introduce chemically synthesized pre-miRNAs (syn-pre-miRNAs) as a general class of accessible, easily transfectable mimics of premiRNAs. These are RNA hairpins, identical in sequence to natural pre-miRNAs. They differ from commercially available miRNA mimics through their complete hairpin structure, including any regulatory elements in their terminal-loop regions and their potential to introduce both strands into RISC. They are distinguished from transcribed pre-miRNAs by their terminal 5′ hydroxyl groups and their precisely defined terminal nucleotides. We demonstrate with several examples how they fully recapitulate the properties of pre-miRNAs, including their processing by Dicer into functionally active 5p-and 3p-derived mature miRNAs. We use syn-pre-miRNAs to show that miR-34a uses its 5p and 3p miRNAs in two pathways: apoptosis during TGF-β signaling, where SIRT1 and SP4 are suppressed by miR-34a-5p and miR-34a-3p, respectively; and the lipopolysaccharide (LPS)-activation of primary human monocyte-derived macrophages, where TNF (TNFα) is suppressed by miR-34a-5p indirectly and miR-34a-3p directly. Our results add to growing evidence that the use of both arms of a miRNA may be a widely used mechanism. We further suggest that syn-pre-miRNAs are ideal and affordable tools to investigate these mechanisms.

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Section: Discussioncontrasting

confidence: 71%

Section: Identification Of New Targets For Mir-34a-3pmentioning

confidence: 68%

Section: Identification Of New Targets For Mir-34a-3pmentioning

confidence: 80%

Section: Identification Of New Targets For Mir-34a-3pmentioning

confidence: 98%

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Synthetic pre-microRNAs reveal dual-strand activity of miR-34a on TNF-α

Guennewig

Roos

Dogar

et al. 2013

RNA

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“…Using 450 K high-resolution array, Cahill et al were able to identify that NOTCH1 is differentially methylated between M-CLL and UM-CLL [60]. Additional complexity in multilayered epigenetic regulation comes from the discovery that NOTCH1 is a target of miR34a in many tumor types and that miR34a is hypermethylated in 4 % of CLL cases [87], thus making it likely for NOTCH1 to be overexpressed at least in part due to miR34a downregulation in CLL [88][89][90]. The role of NOTCH1 in the pathogenesis of CLL and the mechanisms of its epigenetic deregulation is subject to further investigation.…”

Section: Single Gene Silencing In Cll By Hypermethylationmentioning

confidence: 99%

Gene Expression and Epigenetic Deregulation

Shaknovich

2013

Advances in Experimental Medicine and Biology

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The last decade resulted in many scientific discoveries illuminating epigenetic mechanisms of gene regulation and genome organization. DNA methylation emerged as playing a pivotal role in development and cancer. Genome-wide changes in DNA methylation, including hypermethylation of tumor suppressor genes and genome-wide loss of methylation, are two dominant mechanisms that deregulate gene expression and contribute to chromosomal instability. In this chapter we give an overview of how methylation patterns are established during B-cell development and what machinery is necessary to maintain those patterns. We summarize the current state of knowledge of aberrant changes taking place during and contributing to lymphoid transformation in general and to the development of CLL in particular. We discuss key deregulated biomarkers extensively studied using single-gene approaches and give an overview of a wealth of data that became available from genome-wide approaches, focusing on pathways that are critical for lymphomagenesis. We also highlight epigenetic differences between known prognostic groups of CLL.

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