Depletion of STAT6 suppresses lung cancer progression through regulating M2-macrophage polarization

2018 ◽  
Author(s):  
Cuiping Fu ◽  
Shanqun Li
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization

scholarly journals Hypoxic Tumor-Derived Exosomes Induce M2 Macrophage Polarization via AMPK/p38 To Promote Lung Cancer Progression

2021 ◽  
Author(s):  
Shiyu Zhou ◽  
Yu Lan ◽  
Yuqun Li ◽  
Zhenxing Li ◽  
Jinding Pu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Western Blot ◽  
Cancer Progression ◽  
Macrophage Polarization ◽  
A549 Cells ◽  
M2 Macrophage ◽  
Mesenchymal Transition ◽  
M2 Polarization ◽  
M2 Macrophage Polarization ◽  
P38 Pathway

Abstract Background Hypoxia is a major regulator of tumor aggressiveness and metastasis in cancer progression. Exosomes (exos) play an important role in the communication between lung cancer and hypoxic microenvironment. However, the underlying mechanisms are largely undefined. Methods Exos isolated from A549 cells under hypoxia conditions. Transmission electron microscopy and nanoparticle tracking analysis were carried out to characterize exos. CCK-8 assay, flow cytometry, Western blot, wound healing and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of A549 cells, respectively. The M2 polarization of macrophages was evaluated by RT-qPCR and Western blot analysis. In vivo nude mice model was established to determine the regulatory effect of hypoxia/exos on the progression of lung cancer. Results Hypoxic A549 cell-derived exos (hypoxia/exos) promoted the proliferation and migration, and inhibited the apoptosis in A549 cells. The expression of PKM2 was significantly upregulated in hypoxia/exos. Hypoxic exosomal PKM2 induced M2 polarization of macrophages by activating AMPK/p38 pathway. Co-culture with hypoxia/exos-treated macrophages enhanced the migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. Moreover, treatment with hypoxia/exos facilitated the tumor growth and lung metastasis of A549 cells. Conclusions Our findings reveal that hypoxic exosomal PKM2 induces M2 macrophage polarization via AMPK/p38 pathway, and thus exerts a simulative effect on the growth and metastasis of lung carcinoma.

scholarly journals Tumor Cell-Derived Exosomal miR-770 Inhibits M2 Macrophage Polarization via Targeting MAP3K1 to Inhibit the Invasion of Non-small Cell Lung Cancer Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Jixian Liu ◽  
Ruixing Luo ◽  
Junbin Wang ◽  
Xinyu Luan ◽  
Da Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cell ◽  
Macrophage Polarization ◽  
Small Cell ◽  
Nsclc Cell ◽  
M2 Macrophage ◽  
Small Cell Lung ◽  
Bioinformatics Tool ◽  
M2 Macrophage Polarization

BackgroundNon-small cell lung carcinoma (NSCLC) is a type lung cancer with high malignant behaviors. MicroRNAs (miRNAs) are known to be involved in progression of NSCLC. In order to explore potential targets for the treatment of NSCLC, bioinformatics tool was used to analyze differential expressed miRNAs between NSCLC and adjacent normal tissues.MethodsBioinformatics tool was used to find potential targets for NSCLC. Cell proliferation was investigated by Ki67 staining. Cell apoptosis was measured by flow cytometry. mRNA and protein expression in NSCLC cells were detected by RT-qPCR and Western-blot, respectively. Transwell assay was performed to test the cell migration and invasion. In order to investigate the function of exosomal miRNA in NSCLC, in vivo model of NSCLC was constructed.ResultsMiR-770 was identified to be downregulated in NSCLC, and miR-770 agomir could significantly inhibit NSCLC cell proliferation through inducing the apoptosis. Additionally, the metastasis of NSCLC cells was decreased by miR-770 agomir. MAP3K1 was identified to be the target mRNA of miR-770. Meanwhile, tumor cell-derived exosomal miR-770 inhibited M2 macrophage polarization via downregulation of MAP3K1, which in turn suppressed NSCLC cell invasion. Besides, tumor cell-derived exosomal miR-770 markedly decreased NSCLC tumor growth in vivo through suppressing M2 macrophage polarization.ConclusionTumor cell-derived exosomal miR-770 inhibits M2 macrophage polarization to inhibit the invasion of NSCLC cells via targeting MAP3K1. Thus, this study provided a new strategy for the treatment of NSCLC.

scholarly journals LINC00467 Promotes Prostate Cancer Progression via M2 Macrophage Polarization and the miR-494-3p/STAT3 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao Jiang ◽  
Wen Deng ◽  
Ke Zhu ◽  
Zhenhao Zeng ◽  
Bing Hu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Macrophage Polarization ◽  
Migration And Invasion ◽  
M2 Macrophage ◽  
Prostate Cancer Progression ◽  
Cycle Progression ◽  
M2 Macrophage Polarization

BackgroundThe long non-coding RNA LINC00467 plays a vital role in many malignancies. Nevertheless, the role of LINC00467 in prostate carcinoma (PC) is unknown. Herein, we aimed to explore the mechanism by which LINC00467 regulates PC progression.MethodsWe used bioinformatics analyses and RT-qPCR to investigate the expression of LINC00467 in PC tissues and cells. The function of LINC00467 in the progression of PC was confirmed by loss-of-function experiments. PC cell proliferation was assessed by CCK-8 and EdU assays. The cell cycle progression of PC cells was examined by flow cytometry. Moreover, Transwell assays were used to investigate the migration and invasion of PC cells. Western blot assays were used to detect the expression of factors associated with epithelial–mesenchymal transition. The interactions of LINC00467 with prostate cancer progression and M2 macrophage polarization were confirmed by RT-qPCR. The subcellular localization of LINC00467 was investigated via the fractionation of nuclear and cytoplasmic RNA. Bioinformatics data analysis was used to predict the correlation of LINC00467 expression with miR-494-3p expression. LINC00467/miR-494-3p/STAT3 interactions were identified by using a dual-luciferase reporter system. Finally, the influence of LINC00467 expression on PC progression was investigated with an in vivo nude mouse model of tumorigenesis.ResultsWe established that LINC00467 expression was upregulated in PC tissues and cells. Downregulated LINC00467 expression inhibited PC cell growth, cell cycle progression, migration, and invasion. Downregulated LINC00467 expression similarly inhibited PC cell migration via M2 macrophage polarization. Western blot analysis showed that LINC00467 could regulate the STAT3 pathway. We established that LINC00467 is mainly localized to the cytoplasm. Bioinformatics analysis and rescue experiments indicated that LINC00467 promotes PC progression via the miR-494-3p/STAT3 axis. Downregulated LINC00467 expression was also able to suppress PC tumor growth in vivo.ConclusionsOur study reveals that LINC00467 promotes prostate cancer progression via M2 macrophage polarization and the miR-494-3p/STAT3 axis.

scholarly journals A double feedback loop mediated by microRNA-23a/27a/24-2 regulates M1 versus M2 macrophage polarization and thus regulates cancer progression

Oncotarget ◽  
2015 ◽  
Vol 7 (12) ◽  
pp. 13502-13519 ◽  
Author(s):  
Sisi Ma ◽  
Min Liu ◽  
Zhenbiao Xu ◽  
Yanshuang Li ◽  
Hui Guo ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Feedback Loop ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization

scholarly journals Ovarian Cancer Cell-Derived Exosomal miR-205 Promotes M2 Macrophage Polarization and Ovarian Cancer Cell Metastasis By Activating The AKT/mTOR Signalling Pathway

2021 ◽  
Author(s):  
Liuqing He ◽  
Quan Chen ◽  
Di Wu ◽  
Wei Zhu ◽  
Qifeng Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ovarian Cancer Cell ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Qrt Pcr ◽  
M2 Macrophage Polarization

Abstract Background: Tumour-associated macrophages (TAMs) are the most abundant immune cells in the tumour environment and are considered to be similar to M2 macrophages, which facilitate cancer progression. Exosomes, as important mediators of cell-to-cell communication, can alter the phenotype of TAMs by transferring microRNAs (miRNAs) that influence targets and signalling pathways. However, the exact mechanisms by which cancer-derived exosomal miRNAs facilitate the development and metastasis of ovarian cancer (OC) remain unclear.Methods: In situ hybridization and immunohistochemistry were performed to examine the relationship between miR-205 and CD163 in OC. Exosome labelling experiments and qRT-PCR were used to detect the transfer of miR-205 from OC cells to macrophages. The effects of exosomal miR-205-induced macrophages on OC cell migration, invasion and EMT were assessed by in vitro assays in a co-culture model. Western blotting and qRT-PCR experiments were performed to investigate the role of the PI3K/AKT/mTOR axis in M2 macrophage polarization induced by exosomal miR-205. An in vivo mouse tumour model was used to evaluate the effects of M2 macrophages induced by exosomal miR-205.Results: We found that miR-205 expression levels were associated with M2 macrophage infiltration in patients with OC. miR-205 could be transported from OC cells to macrophages via exosomes and altered the macrophage phenotype. Moreover, macrophages that received exosomal miR-205 further enhanced the invasion, migration and EMT of OC cells. Decreased PTEN levels caused by exosomal miR-205 could increase the activation of AKT and mTOR as well as the expression of several immunosuppressive factors. In contrast, inhibition of miR-205 or restoration of PTEN effectively decreased cancer-mediated M2-type polarization, improving the infiltration of inflammatory factors in the tumour environment. Exosomal miR-205 derived from OC cells was found to induce M2-type polarization of macrophages and promote cancer progression in vivo.Conclusions: These results suggest a novel mechanism by which exosomal miR-205 induces M2 macrophage polarization and facilitates OC progression by targeting the PI3K/AKT/mTOR axis. Targeting exosomal miR-205 may offer a potential diagnosis and treatment strategy for OC.

Sign in / Sign up

Export Citation Format

Share Document