MicroRNA-146a and MicroRNA-146b Regulate Human Dendritic Cell Apoptosis and Cytokine Production by Targeting TRAF6 and IRAK1 Proteins

Park, Haein; Huang, Xin; Lu, Changming; Cairo, Mitchell S.; Zhou, Xianzheng

doi:10.1074/jbc.m114.591420

Cited by 213 publications

(161 citation statements)

References 45 publications

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…As a result, we found that miR-146b-5p regulated many other cancer-related genes combined with several TFs. Especially, genes BRCA1, IRAK1, and NFKB1 were confirmed targets of miR-146b-5p by previous studies (22,23).…”

Section: Mirna and Tf Regulation Of Cancer Genes And Pathwaysmentioning

confidence: 75%

miR-146b-5p within BCR-ABL1–Positive Microvesicles Promotes Leukemic Transformation of Hematopoietic Cells

Zhang

Zhu

et al. 2016

Cancer Research

View full text Add to dashboard Cite

Evidence is accumulating that extracellular microvesicles (MV) facilitate progression and relapse in cancer. Using a model in which MVs derived from K562 chronic myelogenous leukemia (CML) cells transform normal hematopoietic transplants into leukemia-like cells, we defined the underlying mechanisms of this process through gene-expression studies and network analyses of transcription factors (TF) and miRNAs. We found that antitumor miRNAs were increased and several defense pathways were initiated during the early phases of oncogenic transformation. Later, oncomiRs and genes involved in cell cycle, DNA repair, and energy metabolism pathways were upregulated. Regulatory network analyses revealed that a number of TFs and miRNAs were responsible for the pathway dysregulation and the oncogenic transformation. In particular, we found that miR-146b-5p, which was highly expressed in MVs, coordinated the regulation of cancer-related genes to promote cell-transforming processes. Notably, treatment of recipient cells with MV derived from K562 cells expressing mimics of miR-146b-5p revealed that it accelerated the transformation process in large part by silencing the tumor-suppressor NUMB. High levels of miR-146b-5p also enhanced reactive oxygen species levels and genome instability of recipient cells. Taken together, our finding showed how upregulation of oncogenic miRNAs in MVs promote hematopoetic cells to a leukemic state, as well as a demonstration for TF and miRNA coregulatory analysis in exploring the dysregulation of cancers and discovering key factors. Cancer Res; 76(10); 2901-11. Ó2016 AACR.

show abstract

Section: Mirna and Tf Regulation Of Cancer Genes And Pathwaysmentioning

confidence: 75%

miR-146b-5p within BCR-ABL1–Positive Microvesicles Promotes Leukemic Transformation of Hematopoietic Cells

Zhang

Zhu

et al. 2016

Cancer Research

View full text Add to dashboard Cite

show abstract

“…Consistent with this hypothesis, TRAF6 expression was decreased in miR-146b transgenic mice, 26 and inversely correlated with miR-146b-5p expression in umbilical vein endothelial cells (HUVECs) and dendritic cells (DCs). 42,43 To confirm the predicted miR-146b-5p binding site in TRAF6, HEK293 cells were transiently transfected with pGL3 firefly luciferase (ff-luc)reporter plasmids with no insert, or with the wild-type (WT) or mutated (MUT) 39 UTR sequences of TRAF6 (supplemental Table 1 …”

Section: Resultsmentioning

confidence: 99%

miR-146b antagomir–treated human Tregs acquire increased GVHD inhibitory potency

Hippen

Lemire

et al. 2016

Blood

View full text Add to dashboard Cite

show abstract

“…A study in miR-146a knockout mice has shown that these mice produce an excessive amount of pro-inflammatory cytokines after bacterial challenge (38). A recent study showed that the expression of miR-146a and miR146b is increased when monocytes differentiate into dendritic cells (39). Silencing of these two miRNAs enhances the expression of pro-inflammatory cytokines Il-12, Il-6, and Ifn-␥ (39).…”

Section: Discussionmentioning

confidence: 99%

RNA-seq Analysis of δ9-Tetrahydrocannabinol-treated T Cells Reveals Altered Gene Expression Profiles That Regulate Immune Response and Cell Proliferation

Yang

Bam

Nagarkatti

2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Marijuana has drawn significant public attention and concern both for its medicinal and recreational use. ⌬9-Tetrahydrocannabinol (THC), which is the main bioactive component in marijuana, has also been shown to possess potent anti-inflammatory properties by virtue of its ability to activate cannabinoid receptor-2 (CB-2) expressed on immune cells. In this study, we used RNA-seq to quantify the transcriptomes and transcript variants that are differentially regulated by THC in super antigen-activated lymph node cells and CD4 ؉ T cells. We found that the expressions of many transcripts were altered by THC in both total lymph node cells and CD4 ؉ T cells. Furthermore, the abundance of many miRNA precursors and long non-coding RNAs was dramatically altered in THC-treated mice. For example, the expression of miR-17/92 cluster and miR-374b/421 cluster was down-regulated by THC. On the other hand miR146a, which has been shown to induce apoptosis, was up-regulated by THC. Long non-coding RNAs that are expressed from the opposite strand of CD27 and Appbp2 were induced by THC. In addition, THC treatment also caused alternative promoter usage and splicing. The functions of those altered transcripts were mainly related to immune response and cell proliferation.Marijuana (Cannabis sativa) is the most widely used drug of abuse in the United States. Nonetheless, it is worth noting that its medicinal value has been known for many centuries and is getting increasing recognition in recent times. Thus, ⌬9-tetrahydrocannabinol (THC), 2 the major psychoactive principle in marijuana, is used for medicinal purposes such as for pain relief as well as an anti-emetic and appetite stimulant during cancer chemotherapy and in HIV/AIDS patients (1). In addition, marijuana is widely known anecdotally for its use to relieve pain, and prevent seizures in patients with epilepsy. Because of the potential therapeutic value of marijuana in a variety of clinical disorders, 23 states and the District of Columbia currently have laws legalizing marijuana for medicinal use. Four states and the District of Columbia have also legalized marijuana for recreational use. Clearly, legalization of marijuana for medicinal or recreational purposes raises significant questions on its long term use/abuse and the impact on human health.THC has also been shown to modulate immune response primarily through activation of cannabinoid receptors (CB2) expressed primarily on cells of the immune system (2-4). In general, most studies have shown that THC has immunosuppressive properties mediated through multiple pathways (2, 5, 6). For example, it has been shown that THC suppresses Th1, whereas promoting Th2 cells (7). THC has also been shown to induce apoptosis in immune cells (8, 9), and induce myeloidderived suppressor cells and Tregs, which are known to inhibit T cell proliferation (10 -12). Moreover, induction of myeloidderived suppressor cell by THC is associated with altered microRNA expression (13). Our previous studies have shown that epigenetic modifications such as...

show abstract

MicroRNA-146a and MicroRNA-146b Regulate Human Dendritic Cell Apoptosis and Cytokine Production by Targeting TRAF6 and IRAK1 Proteins

Cited by 213 publications

References 45 publications

miR-146b-5p within BCR-ABL1–Positive Microvesicles Promotes Leukemic Transformation of Hematopoietic Cells

miR-146b-5p within BCR-ABL1–Positive Microvesicles Promotes Leukemic Transformation of Hematopoietic Cells

miR-146b antagomir–treated human Tregs acquire increased GVHD inhibitory potency

RNA-seq Analysis of δ9-Tetrahydrocannabinol-treated T Cells Reveals Altered Gene Expression Profiles That Regulate Immune Response and Cell Proliferation

Contact Info

Product

Resources

About