miRNA let-7b modulates macrophage polarization and enhances tumor-associated macrophages to promote angiogenesis and mobility in prostate cancer

Wang, Zhigang; Xu, Lu; Hu, Yinying; Huang, Yanqin; Zhang, Yujuan; Zheng, Xiufen; Wang, Shanshan; Wang, Yifan; Yu, Yan-Rong; Zhang, Meng; Yuan, Keng; Min, Wei‐Ping

doi:10.1038/srep25602

Cited by 82 publications

(67 citation statements)

References 49 publications

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“…When addressing the “exclusive lung interactions” the genes CDT1, CENPN, DAPK2, HJURP, KIF20A, NACPD2, NCAPG, NCAPH, SMC1B , and SPC24 have so far not been associated to survival in lung cancer, although most of its associated miRNAs have been. For instance miR-miR-1976 and miR-let-7b-5p miRNAs had already been associated to prognosis in lung cancer4969, and in other tumours like breast70, prostate71, and gastric72. In conclusion, our analysis has revealed novel miRNA-gene correlations that associate with patient prognosis, supported by previous findings on different tumour types.…”

Section: Discussionsupporting

confidence: 87%

Novel miRNA-mRNA interactions conserved in essential cancer pathways

Andrés-León

Cases²,

Alonso

et al. 2017

Sci Rep

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Cancer is a complex disease in which unrestrained cell proliferation results in tumour development. Extensive research into the molecular mechanisms underlying tumorigenesis has led to the characterization of oncogenes and tumour suppressors that are key elements in cancer growth and progression, as well as that of other important elements like microRNAs. These genes and miRNAs appear to be constitutively deregulated in cancer. To identify signatures of miRNA-mRNA interactions potentially conserved in essential cancer pathways, we have conducted an integrative analysis of transcriptomic data, also taking into account methylation and copy number alterations. We analysed 18,605 raw transcriptome samples from The Cancer Genome Atlas covering 15 of the most common types of human tumours. From this global transcriptome study, we recovered known cancer-associated miRNA-targets and importantly, we identified new potential targets from miRNA families, also analysing the phenotypic outcomes of these genes/mRNAs in terms of survival. Further analyses could lead to novel approaches in cancer therapy.

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Section: Discussionsupporting

confidence: 87%

Novel miRNA-mRNA interactions conserved in essential cancer pathways

Andrés-León

Cases²,

Alonso

et al. 2017

Sci Rep

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“…Among the members of the let-7 family, let-7b and let-7f promote angiogenesis by suppressing two important inhibitors of cellular migration: Tissue inhibitor of metalloproteinase 1 (TIMP-1) and Tsp 1 and 2 [66,67]. In prostate cancer, let-7b regulates macrophage polarization and enhances tumor-associated macrophages to stimulate angiogenesis by modulating the expression profile of inflammatory cytokines such as interleukin (IL)-12, IL-23, IL-10, and tumor necrosis factor-α [68].…”

Section: Lethal (Let)-7b and -7fmentioning

confidence: 99%

Insights into the Regulation of Tumor Angiogenesis by Micro-RNAs

Leone

Buonavoglia

Fasano

et al. 2019

JCM

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One of the hallmarks of cancer is angiogenesis, a series of events leading to the formation of the abnormal vascular network required for tumor growth, development, progression, and metastasis. MicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs whose functions include modulation of the expression of pro- and anti-angiogenic factors and regulation of the function of vascular endothelial cells. Vascular-associated microRNAs can be either pro- or anti-angiogenic. In cancer, miRNA expression levels are deregulated and typically vary during tumor progression. Experimental data indicate that the tumor phenotype can be modified by targeting miRNA expression. Based on these observations, miRNAs may be promising targets for the development of novel anti-angiogenic therapies. This review discusses the role of various miRNAs and their targets in tumor angiogenesis, describes the strategies and challenges of miRNA-based anti-angiogenic therapies and explores the potential use of miRNAs as biomarkers for anti-angiogenic therapy response.

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“…Our previous study showed that let-7b is highly expressed in M-CMs, which have an M2-like phenotype 20 .…”

Section: Discussionmentioning

confidence: 98%

“…Our previous results indicated that conditioned media from PC-3 PCa cells can induce macrophages to differentiate into M2 macrophages, a process that is signi cantly associated with the high expression of let-7 20 . Therefore, we focused on let-7b-5p targeting SOCS1/STAT in macrophages and its role in the progression of PCa.…”

Section: Introductionmentioning

confidence: 96%

Inhibition of let-7b-5p contributes to anti-tumorigenic macrophage phenotype through SOCS1/STAT pathway in prostate cancer

Rong

et al. 2020

Preprint

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BackgroundDysfunction of microRNAs (miRNAs) is a major cause of aberrant expression of inflammatory cytokines and contributes to macrophage polarization. Previous studies have shown that miRNA let-7 is associated with cell differentiation, and the expression of let-7b-5p is significantly increased in M2 macrophages. However, the mechanism by which let-7b-5p regulates macrophage differentiation in prostate cancer (PCa) remains largely unknown.MethodsHuman macrophages were induced by the blood monocytes from healthy male donors. M1 macrophages were polarized by stimulating overnight with 100 ng/ml lipopolysaccharides and 100 ng/ml IFN-γ, while conditioned medium from PC-3 cells were used to induce prostatic macrophages (M-CMs) in vitro, and then let-7b-5p mimics or inhibitors were transfected into M1 and M-CMs for 72 hours respectively. The expression of cluster of differentiation 206 (CD206) in each group was detected by a High Throughput Connotation of Imaging System. Quantitative real-time polymerase chain reaction (qRT-PCR) was executed to examine the expression of inflammatory cytokines IL-10, IL-12, IL-13, TNF-alpha and let-7b in macrophages. SOCS1 protein level was evaluated by ELISA, and the phosphorylation difference of STAT family member proteins was analysized by CST signal pathway chip. Phagocytosis of macrophages and the effect of macrophages on the proliferation of prostate cancer cell PC-3 were evaluated by phagocytosis assay or Cell Counting Kit-8 (CCK-8). The relationship between SOCS1 and let-7b-5p was confirmed with the dual-luciferase reporter.ResultsThe expression of cluster of differentiation 206 (CD206), an M2-like macrophage surface molecule, was significantly increased in M1 macrophages treated with let-7b-5p mimics, while CD206 expression was decreased in M-CMs treated with let-7b-5p inhibitors. Overexpression or knockdown of let-7b-5p significantly affected the expression of inflammatory factors in macrophages including interleukin 10 (IL-10), IL-12, IL-13, and tumor necrosis factor alpha. Let-7b-5p downregulated the expression of suppressor of cytokine signaling 1 (SOCS1) and increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5a proteins in M-CMs and M1 macrophages with let-7b-5p mimics compared with the other groups. In addition, with high expression of let-7b-5p, the phagocytosis of macrophages showed a significant decrease. As a result, M-CMs treated with let-7b-5p inhibitors reduced the proliferation of PC-3 PCa cells.ConclusionsCollectively, these data indicate that let-7b-5p may regulate M2 polarization through the SOCS1/STAT pathway, and reversal of M2 differentiation by let-7b-5p inhibitors can enhance macrophage phagocytosis, ultimately inhibiting the proliferation of PCa cells.Trial registrationNot applicable

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miRNA let-7b modulates macrophage polarization and enhances tumor-associated macrophages to promote angiogenesis and mobility in prostate cancer

Cited by 82 publications

References 49 publications

Novel miRNA-mRNA interactions conserved in essential cancer pathways

Novel miRNA-mRNA interactions conserved in essential cancer pathways

Insights into the Regulation of Tumor Angiogenesis by Micro-RNAs

Inhibition of let-7b-5p contributes to anti-tumorigenic macrophage phenotype through SOCS1/STAT pathway in prostate cancer

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