Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway

Zhang, Wei; Zheng, Xiaoxiao; Yu, Yingning; Zheng, Lirong; Lan, Jiahua; Wu, Ying; Líu, Hao; An, Zhen; Huang, Hang; Chen, Wei

doi:10.7150/ijbs.70289

Cited by 51 publications

(41 citation statements)

References 35 publications

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“…Exosomes derived from renal cell carcinoma cells were reported to promote macrophage polarization, cytokine release, phagocytosis, angiogenesis, and tumor development. Overexpression of long noncoding RNA ARSR induced phenotypic and functional changes of macrophages in vitro and promoted tumor growth in vivo , while knockout of long noncoding RNA ARSR impaired the exosome-mediated polarization of macrophages [ 37 ]. Luo et al established an in vitro cell model and an in vivo mouse model of Mycobacterium tuberculosis infection and conducted negative pressure treatment.…”

Section: Discussionmentioning

confidence: 99%

The Long Noncoding RNA Gm9866/Nuclear Factor-κB Axis Promotes Macrophage Polarization

Liao

Ruan

Chen

et al. 2023

Mediators of Inflammation

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Macrophages are a type of immune cells with high levels of plasticity and heterogeneity. They can polarize into M1 or M2 functional phenotypes. These two phenotypes exhibit a dynamic balance during polarization-related diseases and play opposing roles. Long noncoding RNAs (lncRNAs) play an important role in biological processes such as cell proliferation, death, and differentiation; however, how long noncoding RNAs affect the cellular functionality of macrophages remains to be studied. Long noncoding RNA Gm9866 was found to be closely related to macrophage polarization through bioinformatics analysis. In this study, by conducting real-time polymerase chain reaction analysis, it was observed that long noncoding RNA Gm9866 expression significantly increased after treatment with interleukin-4 but significantly decreased after treatment with lipopolysaccharide. Fluorescence in situ hybridization revealed that long noncoding RNA Gm9866 was expressed mainly in the nucleus. Real-time polymerase chain reaction analysis showed that overexpression of long noncoding RNA Gm9866 in RAW264.7 cells further promoted the expression of M2 markers MRC1 (macrophage mannose receptor 1) and MRC2 (macrophage mannose receptor 2). Western blotting analysis demonstrated inhibition of nuclear factor-κB (NF-κB) expression. EdU (5-ethynyl-2 ′ -deoxyuridine) and TUNEL (TdT-mediated dUTP nick-end labeling) staining assays revealed that overexpression of long noncoding RNA Gm9866 promoted cell proliferation and inhibited apoptosis. These findings thus indicated that long noncoding RNA Gm9866 promoted macrophage polarization and inhibited the nuclear factor-κB signaling pathway. Thus, long noncoding RNA Gm9866 may serve as a potential diagnostic and therapeutic target for polarization-related diseases such as infectious diseases, inflammatory diseases, liver fibrosis, and tumors.

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Section: Discussionmentioning

confidence: 99%

The Long Noncoding RNA Gm9866/Nuclear Factor-κB Axis Promotes Macrophage Polarization

Liao

Ruan

Chen

et al. 2023

Mediators of Inflammation

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“…found that the knockdown of lncRNA PCAT6 could prevent its positive effect on M2 polarization and in turn accelerated NSCLC development ( 75 ). lncARSR-containing EVs derived from renal cell carcinoma achieve a similar effect via the STAT3 pathway ( 76 ). MiR-147a/ARID3A axis is activated under hypoxia condition by hepatocellular carcinoma (HCC)-derived EVs delivering lncRNA HMMR-AS1 ( 77 ).…”

Section: Macrophagementioning

confidence: 99%

Tumor-derived extracellular vesicles modulate innate immune responses to affect tumor progression

et al. 2022

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Immune cells are capable of influencing tumor progression in the tumor microenvironment (TME). Meanwhile, one mechanism by which tumor modulate immune cells function is through extracellular vesicles (EVs), which are cell-derived extracellular membrane vesicles. EVs can act as mediators of intercellular communication and can deliver nucleic acids, proteins, lipids, and other signaling molecules between cells. In recent years, studies have found that EVs play a crucial role in the communication between tumor cells and immune cells. Innate immunity is the first-line response of the immune system against tumor progression. Therefore, tumor cell-derived EVs (TDEVs) which modulate the functional change of innate immune cells serve important functions in the context of tumor progression. Emerging evidence has shown that TDEVs dually enhance or suppress innate immunity through various pathways. This review aims to summarize the influence of TDEVs on macrophages, dendritic cells, neutrophils, and natural killer cells. We also summarize their further effects on the progression of tumors, which may provide new ideas for developing novel tumor therapies targeting EVs.

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“…They demonstrated that exosomal miR-549a could reduce the expression level of hypoxia-inducible factor 1 alpha subunit (HIF1α) by binding to the 3’-UTR region of HIF1α mRNA, which in turn attenuate tumor angiogenesis and endothelial cell migration in ccRCC ( 31 ). A new study found that ccRCC-derived exosomes can activate the miR34/miR449-STAT3 signaling pathway by delivering lncARSR, which in turn promotes the transformation of M1 macrophages to M2 and enhances the phagocytic ability of macrophages, which in turn induces angiogenesis and ultimately promotes the development and progression of tumors ( 32 ). In summary, ccRCC cell-derived exosomes participate in tumor angiogenesis by delivering a variety of miRNA and protein molecules, thereby affecting the metastasis process of ccRCC.…”

Section: Tumor-derived Exosomes Promote Metastasis Of Ccrccmentioning

confidence: 99%

Role of tumor-derived exosomes in metastasis, drug resistance and diagnosis of clear cell renal cell carcinoma

et al. 2022

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Renal cancer is one of the most extensively studied human tumors today, with clear cell renal cell carcinoma accounting for approximately 80% of all cases. Despite recent advances in research on clear cell renal cell carcinoma, advanced distant metastasis of the disease, delay in diagnosis, as well as drug resistance remain major problems. In recent years, as an important mediator of material and information exchange between cells in the tumor microenvironment, exosomes have attracted widespread attention for their role in tumor development. It has been reported that tumor-derived exosomes may act as regulators and have an important effect on the metastasis, drug resistance formation, and providing targets for early diagnosis of clear cell renal cell carcinoma. Therefore, the extensive study of tumour-derived exosomes will provide a meaningful reference for the development of the diagnostic and therapeutic field of clear cell renal cell carcinoma. This article reviews the biological role and research progress of tumor-derived exosomes in different aspects of premetastatic niche formation, tumor angiogenesis, and epithelial-mesenchymal transition during the progression of clear cell renal cell carcinoma. In addition, the role of tumor-derived exosomes in the development of drug resistance in clear cell renal cell carcinoma is also addressed in this review. Furthermore, recent studies have found that cargoes of exosomes in serum and urine, for example, a series of miRNAs, have the potential to be biological markers of clear cell renal cell carcinoma and provide meaningful targets for early diagnosis and monitoring of tumors, which is also covered in this article.

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Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway

Cited by 51 publications

References 35 publications

The Long Noncoding RNA Gm9866/Nuclear Factor-κB Axis Promotes Macrophage Polarization

The Long Noncoding RNA Gm9866/Nuclear Factor-κB Axis Promotes Macrophage Polarization

Tumor-derived extracellular vesicles modulate innate immune responses to affect tumor progression

Role of tumor-derived exosomes in metastasis, drug resistance and diagnosis of clear cell renal cell carcinoma

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