MicroRNA-223 Regulates the Differentiation and Function of Intestinal Dendritic Cells and Macrophages by Targeting C/EBPβ

Zhou, Haibo; Xiao, Jing; Wu, Ning; Liu, Chunxi; Xu, Jie; Liu, Fang; Wu, Li

doi:10.1016/j.celrep.2015.09.073

Cited by 93 publications

(95 citation statements)

References 54 publications

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“…Interestingly, treadmill exercise training also down-regulated the C/EBP␤ expression in hearts (Fig. 8F), which is consistent with our miR-223 TG mouse model as well as previous publication (16). Thus, miR-223-induced physiological hypertrophy also may be attributed to the reduction of C/EBP␤.…”

Section: Volume 291 • Number 30 • July 22 2016supporting

confidence: 79%

“…Nonetheless, recent work has implicated that several bona fide targets of miR-223 (e.g. IGF-1R and C/EBP␤) (15,16) are associated with physiological cardiac hypertrophy, but their functional consequences appear to be counteracted. For example, up-regulation or activation of IGF-1R has been widely proposed to facilitate developmental growth and physiological hypertrophy of the heart (17,18).…”

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confidence: 99%

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Overexpression of miR-223 Tips the Balance of Pro- and Anti-hypertrophic Signaling Cascades toward Physiologic Cardiac Hypertrophy

Yang

Wang

et al. 2016

Journal of Biological Chemistry

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MicroRNAs (miRNAs) have been extensively examined in pathological cardiac hypertrophy. However, few studies focused on profiling the miRNA alterations in physiological hypertrophic hearts. In this study we generated a transgenic mouse model with cardiac-specific overexpression of miR-223. Our results showed that elevation of miR-223 caused physiological cardiac hypertrophy with enhanced cardiac function but no fibrosis. Using the next generation RNA sequencing, we observed that most of dys-regulated genes (e.g. Atf3/5, Egr1/3, Sfrp2, Itgb1, Ndrg4, Akip1, Postn, Rxfp1, and Egln3) in miR-223-transgenic hearts were associated with cell growth, but they were not directly targeted by miR-223. Interestingly, these dysregulated genes are known to regulate the Akt signaling pathway. We further identified that miR-223 directly interacted with 3-UTRs of FBXW7 and Acvr2a, two negative regulators of the Akt signaling. However, we also validated that miR-223 directly inhibited the expression of IGF-1R and ␤1-integrin, two positive regulators of the Akt signaling. Lastly, Western blotting did reveal that Akt was activated in miR-223-overexpressing hearts. Adenovirus-mediated overexpression of miR-223 in neonatal rat cardiomyocytes induced cell hypertrophy, which was blocked by the addition of MK2206, a specific inhibitor of Akt. Taken together, these data represent the first piece of work showing that miR-223 tips the balance of promotion and inactivation of Akt signaling cascades toward activation of Akt, a key regulator of physiological cardiac hypertrophy. Thus, our study suggests that the ultimate phenotype outcome of a miRNA may be decided by the secondary net effects of the whole target network rather than by several primary direct targets in an organ/tissue.Cardiac hypertrophy is an adaptive mechanism of cardiomyocytes to different forms of injury or stress, such as myocardial infarction, hypertension, and valve disease (pathological) or chronic exercise training (physiological) (1). Both pathological and physiological cardiac hypertrophy types are featured with increased myocyte size, but they have distinct molecular and functional phenotypes (2). Pathological cardiac hypertrophy is often associated with interstitial fibrosis and increased myocyte necrosis/apoptosis, leading to cardiac dysfunction (1, 2). By contrast, exercise training-induced physiological cardiac hypertrophy is characterized by overall normal cardiac structure and function, presenting an adaptive beneficial response (1, 2). Indeed, exercise training is clinically recommended as the most effective non-pharmacological intervention to reduce cardiovascular disease (2). Thus, elucidating the molecular mechanisms underlying physiological cardiac hypertrophy would help us identify novel therapies for the treatment of cardiovascular disease.MicroRNAs (miRNAs) 3 are small, endogenous, non-coding RNAs of ϳ22 to 26 nucleotides in length that function primarily as post-transcriptional regulators (3). Importantly, a single miRNA does not only regulate one gene ...

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Section: Volume 291 • Number 30 • July 22 2016supporting

confidence: 79%

mentioning

confidence: 99%

Overexpression of miR-223 Tips the Balance of Pro- and Anti-hypertrophic Signaling Cascades toward Physiologic Cardiac Hypertrophy

Yang

Wang

et al. 2016

Journal of Biological Chemistry

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“…On the other hand, dendritic cell (DC) and macrophages are also crucial in the maintenance of intestinal immune homeostasis . Given the fact that miR‐223 modulates the differentiation of monocytes, several studies have indicated the involvement of miR‐223 in the regulation of innate immunity in IBD . Although miR‐223 deficiency in mice resulted in reduction of CX3CR1hi macrophages at steady state, both CX3CR1 hi macrophage and CD103 + DCs showed a pro‐inflammatory phenotypes.…”

Section: Functional Roles Of Myeloid Mir‐223 During Inflammatory Disementioning

confidence: 99%

MicroRNA miR-223 as regulator of innate immunity

Yuan

Berg

Lee

et al. 2018

Journal of Leukocyte Biology

131

105

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MicroRNAs were discovered more than 2 decades ago and have profound impact on diverse biological processes. Specific microRNAs have important roles in modulating the innate immune response and their dysregulation has been demonstrated to contribute to inflammatory diseases. MiR-223 in particular, is very highly expressed and tightly regulated in hematopoietic cells. It functions as key modulator for the differentiation and activation of myeloid cells. The central role of miR-223 in myeloid cells, especially neutrophil and macrophage differentiation and activation has been studied extensively. MiR-223 contributes to myeloid differentiation by enhancing granulopoiesis while inhibiting macrophage differentiation. Uncontrolled myeloid activation has detrimental consequences in inflammatory disease. MiR-223 serves as a negative feedback mechanism controlling excessive innate immune responses in the maintenance of myeloid cell homeostasis. This review summarizes several topics covering the function of miR-223 in myeloid differentiation, neutrophil and macrophage functions, as well as in inflammatory diseases including acute respiratory distress syndrome and inflammatory bowel disease. In addition, nonmyeloid functions of miR-223 are also discussed in this review. Therapeutic enhancement of miR-223 to dampen inflammatory targets is also highlighted as potential treatment to control excessive innate immune responses during mucosal inflammation.

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“…Research in the mechanism of miR-223 found that it could target C/EBPβ, E2F1, FOXO1, NFI-A, and MAFB to inhibit tumor cell proliferation, migration, and invasive capability in vitro;26–30 however, it could also deregulate the expression of tumor suppressors 31–33. As miR-223 affects multiple targets simultaneously that are involved in key processes,14 the role of miR-223 in cancer depends on the type of cancer and the total level in patient’s body.…”

Section: Discussionmentioning

confidence: 99%

The effect of circulating miR-223 on surveillance of different cancers: a meta-analysis

Zhang

Lin²,

Huang³

et al. 2017

OTT

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PurposeAbnormal expression of miR-223 in cancerous tissue has confirmed it as an important player in tumorigenesis of cancers, such as hepatocellular carcinoma, colorectal carcinoma, osteosarcoma, gastric cancer, and chronic lymphocytic leukemia. The present meta-analysis aimed to explore the association between circulating miR-223 and prognosis of cancers.MethodsThe studies were accessed by an electronic search of multiple databases. RevMan5.3 and STATA14.0 were used to estimate the heterogeneity among studies, pooled effects, and publication bias.ResultsTen studies with data of 1,002 patients with cancer were included in this meta-analysis. The risk of metastasis from stages 3 to 4 of TNM did not decrease when high versus low circulating expression of miR-223 were compared (pooled odds ratio =0.50, 95% CI: 0.24–1.03). In case of prognosis, the overall survival time was not significantly longer with high circulating miR-223 expression (pooled hazard ratio [HR] =0.64, 95% CI: 0.38–1.11) in all cancer types. However, the overall survival time of chronic lymphocytic leukemia (pooled HR =0.19, 95% CI: 0.07–0.54) increased in subgroup analysis. Moreover, the treatment-free survival of chronic lymphocytic leukemia was significantly increased with high circulating miR-223 expression (pooled HR =0.38, 95% CI: 0.23–0.64).ConclusionCirculating miR-223 was not an effective biomarker in prognosis surveillance in all cancers but in chronic lymphocytic leukemia.

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MicroRNA-223 Regulates the Differentiation and Function of Intestinal Dendritic Cells and Macrophages by Targeting C/EBPβ

Cited by 93 publications

References 54 publications

Overexpression of miR-223 Tips the Balance of Pro- and Anti-hypertrophic Signaling Cascades toward Physiologic Cardiac Hypertrophy

Overexpression of miR-223 Tips the Balance of Pro- and Anti-hypertrophic Signaling Cascades toward Physiologic Cardiac Hypertrophy

MicroRNA miR-223 as regulator of innate immunity

The effect of circulating miR-223 on surveillance of different cancers: a meta-analysis

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