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内质网应激促进乳腺癌细胞释放外泌体circ_0001142并诱导巨噬细胞M2极化以调节肿瘤进展。

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

作者信息

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

机构信息

Department of thyroid and breast surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.

Department of Pancreatic surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.

出版信息

Pharmacol Res. 2022 Mar;177:106098. doi: 10.1016/j.phrs.2022.106098. Epub 2022 Jan 26.

DOI:10.1016/j.phrs.2022.106098
PMID:35091089
Abstract

Breast cancer (BC) has a high morbidity and mortality rate. It is imperative to explore the pathogenesis of BC in order to find potential prognostic biomarkers and therapeutic targets. This study screened and verified the differential expression of circ_0001142 in BC tissues and cell lines through bioinformatics and qRT-PCR. Perform dual luciferase reporter gene assay and pull-down detection to verify the correlation between circ_0001142 and miRNA-361-3p and between miR-361-3p and PIK3CB. QRT-PCR, flow cytometry and ELISA were used to study the regulatory effects and regulatory mechanisms of different treatment groups on macrophage polarization. The role of exosomes circ_0001142 in the tumor microenvironment and its influence on BC growth, metastasis and macrophage polarization were investigated through in vivo and in vitro studies. We first found that circ_0001142 is highly expressed in BC. In addition, ERs promote the secretion of tumor exosomes, enhance the entry of circ_0001142 into macrophages and interfere with the process of autophagy and polarization. Finally, it was found that the circ_0001142/miR-361-3p/PIK3CB pathway plays an important role in the polarization of macrophages.

摘要

乳腺癌(BC)具有较高的发病率和死亡率。探索BC的发病机制以寻找潜在的预后生物标志物和治疗靶点势在必行。本研究通过生物信息学和qRT-PCR筛选并验证了circ_0001142在BC组织和细胞系中的差异表达。进行双荧光素酶报告基因检测和下拉检测以验证circ_0001142与miRNA-361-3p之间以及miR-361-3p与PIK3CB之间的相关性。采用qRT-PCR、流式细胞术和ELISA研究不同治疗组对巨噬细胞极化的调节作用和调节机制。通过体内和体外研究探讨外泌体circ_0001142在肿瘤微环境中的作用及其对BC生长、转移和巨噬细胞极化的影响。我们首次发现circ_0001142在BC中高表达。此外,雌激素受体促进肿瘤外泌体的分泌,增强circ_0001142进入巨噬细胞的能力,并干扰自噬和极化过程。最后,发现circ_0001142/miR-361-3p/PIK3CB通路在巨噬细胞极化中起重要作用。

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