Endoplasmic reticulum stress promotes breast cancer cells to release exosomes circ_0001142 and induces M2 polarization of macrophages to regulate tumor progression

Lu, Chong; Shi, Wei; Hu, Wenjing; Zhao, Yuxi; Zhao, Xiangwang; Fang, Dong; Yue, Xin; Peng, Tao; Liu, Chunping

doi:10.1016/j.phrs.2022.106098

Cited by 40 publications

(28 citation statements)

References 29 publications

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“…Since a large number of M2-type macrophages infiltrate HCC caused by HBV and HCV, and the activation of PI3K-Akt-mTOR pathway is related to the M2 polarization of macrophages (11,24), Through literature review, it was found that 13 differential genes (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36), including mTOR, PIK3CA, AKT2, and PIK3CB, involved in the M2-type polarization of macrophages, according to the genes related to M2-type polarization. We first analyzed the expression of these 13 genes in HBV-HCC and HCV-HCC, and found that mTOR was down-regulated while other genes were up-regulated (Figure S3), which was consistent with the molecular characteristics of macrophage polarization.…”

Section: Correlation Analysis Between Hub Genes and Immune Pathwaymentioning

confidence: 99%

Exploring the molecular mechanism of hepatitis virus inducing hepatocellular carcinoma by microarray data and immune infiltrates analysis

2022

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The number of new cases of hepatocellular carcinoma (HCC) worldwide reached 910,000, ranking the sixth, 80% HCC is associated with viruses, so exploring the molecular mechanism of viral carcinogenicity is imperative. The study showed that both HBV and HCV associated HCC and non-viral HCC have the same molecular phenotype (low gene expression and inhibition of immune pathways), but in the tumor immune micro-environment, there is excessive M2-type macrophage polarization in virus-associated hepatocellular carcinoma. To address this phenomenon, the data sets were analyzed and identified five hub genes (POLR2A, POLR2B, RPL5, RPS6, RPL23A) involved in viral gene expression and associated with PI3K-Akt-mTOR pathway activation by six algorithms. In addition, numerous studies have reported that M2-type macrophages participate in the hepatic fibro-pathological process of the development of HCC and are regulated by the PI3K-Akt-mTOR pathway. On this basis, the study showed that hepatitis virus causes abnormal expression of hub genes, leading to the activation of the pathway, which in turn promote the differentiation of M2-type macrophages and eventually promote the formation of liver fibrosis, leading to the occurrence of HCC. In addition, these hub genes are regulated by transcription factors and m6A enzyme, and have good prognosis and diagnostic value. With regard to drug reuse, the results suggest that patients with virus-related HCC for whom Cytidine triphosphate disodium salt and Guanosine-5’-Triphosphate are used as supplementary therapy, and may have a better prognosis. In conclusion, the study has identified novel molecules that are carcinogenic to hepatitis viruses and are expected to serve as molecular markers and targets for diagnosis and treatment.

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Section: Correlation Analysis Between Hub Genes and Immune Pathwaymentioning

confidence: 99%

Exploring the molecular mechanism of hepatitis virus inducing hepatocellular carcinoma by microarray data and immune infiltrates analysis

2022

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“…Recent studies have shown that ER stress can promote EV secretion in breast cancer cells 11 . Constituting the largest population of structural cells in lung tissues and the cells initially damaged by MV, alveolar epithelial cells were found to be the primary cells secreting EVs in lung tissues during MV.…”

Section: Resultsmentioning

confidence: 99%

ASK1-ER stress pathway-mediated fibrotic-EV release contributes to the interaction of alveolar epithelial cells and lung fibroblasts to promote mechanical ventilation-induced pulmonary fibrosis

Tang

Mei

et al. 2022

Exp Mol Med

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Recent clinical research has revealed that mechanical ventilation (MV) can initiate pulmonary fibrosis and induce mechanical ventilation-induced pulmonary fibrosis (MVPF). However, the underlying mechanism remains largely uncharacterized. Based on a mouse model of MVPF and an alveolar epithelial cell cyclic strain model, the present study explores the possible mechanism of MVPF. Single-cell RNA-sequencing and EV RNA-sequencing analysis revealed that MV promoted apoptosis signal-regulating kinase 1 (ASK1)-mediated endoplasmic reticulum (ER) stress pathway activation and extracellular vesicle (EV) release from alveolar epithelial cells. Furthermore, the ASK1-ER stress pathway was shown to mediate mechanical stretch (MS)- or MV-induced EV release and lung fibroblast activation in vivo and in vitro. These processes were suppressed by ER stress inhibitors or by silencing ASK1 with ASK1- short hairpin RNA (shRNA). In addition, MVPF was suppressed by inhibiting ASK1 and ER stress in vivo. Therefore, the present study demonstrates that ASK1-ER stress pathway-mediated fibrotic-EV release from alveolar epithelial cells contributes to fibroblast activation and the initiation of pulmonary fibrosis during MV. The inhibited release of EVs targeting the ASK1-ER stress pathway might be a promising treatment strategy for MVPF.

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“…It follows that PD-L1 delivered by EVs provides an important target for inhibiting tumor immune escape. In addition to mir-27a-3p, circ_0001142 in EVs was shown to enter tumor-associated Mφs under ER stress, interfere with Mφs autophagy, and induce M2 polarization through the mir-361-3p/PIK3 catalytic subunit beta pathway, thus promoting BC growth and metastasis ( 25 ). These findings suggest that the contents of EVs under ER stress have multiple rather than single targets, and the complex pathogenesis may require simultaneous inhibition of multiple pathways.…”

Section: Cancermentioning

confidence: 99%

Interactions between endoplasmic reticulum stress and extracellular vesicles in multiple diseases

Liu

2022

Front. Immunol.

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Immune responses can severely perturb endoplasmic reticulum (ER) function. As a protein-folding factory and dynamic calcium storage compartment, the ER plays a pivotal role in resisting pathogens and in the development of autoimmune diseases and various other diseases, including cancer, cardiovascular, neurological, orthopedic, and liver-related diseases, metabolic disorders, etc. In recent years, an increasing number of studies have shown that extracellular vesicles (EVs) play important roles in these conditions, suggesting that cells carry out some physiological functions through EVs. The formation of EVs is dependent on the ER. ER stress, as a state of protein imbalance, is both a cause and consequence of disease. ER stress promotes the transmission of pathological messages to EVs, which are delivered to target cells and lead to disease development. Moreover, EVs can transmit pathological messages to healthy cells, causing ER stress. This paper reviews the biological functions of EVs in disease, as well as the mechanisms underlying interactions between ER stress and EVs in multiple diseases. In addition, the prospects of these interactions for disease treatment are described.

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Endoplasmic reticulum stress promotes breast cancer cells to release exosomes circ_0001142 and induces M2 polarization of macrophages to regulate tumor progression

Cited by 40 publications

References 29 publications

Exploring the molecular mechanism of hepatitis virus inducing hepatocellular carcinoma by microarray data and immune infiltrates analysis

Exploring the molecular mechanism of hepatitis virus inducing hepatocellular carcinoma by microarray data and immune infiltrates analysis

ASK1-ER stress pathway-mediated fibrotic-EV release contributes to the interaction of alveolar epithelial cells and lung fibroblasts to promote mechanical ventilation-induced pulmonary fibrosis

Interactions between endoplasmic reticulum stress and extracellular vesicles in multiple diseases

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