miR-382 inhibits breast cancer progression and metastasis by affecting the M2 polarization of tumor-associated macrophages by targeting PGC-1 alpha

作者全名："Zhou, Hua; Gan, Mingyu; Jin, Xin; Dai, Meng; Wang, Yuanyuan; Lei, Youyang; Lin, Zijing; Ming, Jia"

作者地址："[Zhou, Hua] Chongqing Univ, Dept Breast & Thyroid Surg, Affiliated Shapingba Hosp, Chongqing 400030, Peoples R China; [Gan, Mingyu] Shanxi Med Univ, Taiyuan 030607, Shanxi, Peoples R China; [Jin, Xin] Chongqing Univ, Dept Crit Care Med, Affiliated Fuling Hosp, Chongqing 408099, Peoples R China; [Dai, Meng; Wang, Yuanyuan; Lei, Youyang; Lin, Zijing; Ming, Jia] Chongqing Med Univ, Dept Breast & Thyroid Surg, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Ming, Jia] Chongqing Med Univ, Affiliated Hosp 2, Dept Breast & Thyroid Surg, 76 Linjiang Rd, Chongqing 400010, Peoples R China"

通信作者："Ming, J (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Breast & Thyroid Surg, 76 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：INTERNATIONAL JOURNAL OF ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000855167600001

JCR分区：Q1

影响因子：5.2

年份：2022

卷号：61

期号：4

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结束页：　

文献类型：Article

关键词：microRNA; breast cancer; tumor-associated macrophages; tumor microenvironment; metabolic reprogramming

摘要："Macrophages are principal immune cells with a high plasticity in the human body that can differentiate under different conditions in the tumor microenvironment to adopt two polarized phenotypes with opposite functions. Therefore, converting macrophages from the immunosuppressive phenotype (M2) to the inflammatory phenotype (M1) is considered a promising therapeutic strategy for cancer. However, the molecular mechanisms underlying this conversion process have not yet been completely elucidated. In recent years, microRNAs (miRNAs or miRs) have been shown to play key roles in regulating macrophage polarization through their ability to modulate gene expression. In the present study, it was found that miR-382 expression was significantly downregulated in tumor-associated macrophages (TAMs) and M2-polarized macrophages in breast cancer. In vitro, macrophage polarization toward the M2 phenotype and M2-type cytokine release were inhibited by transfection with miR-382-overexpressing lentivirus. Similarly, the overexpression of miR-382 inhibited the ability of TAMs to promote the malignant behaviors of breast cancer cells. In addition, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) was identified as the downstream target of miR-382 and it was found that PGC-1 alpha affected macrophage polarization by altering the metabolic status. The ectopic expression of PGC-1 alpha restored the phenotype and cytokine secretion of miR-382-overexpressing macrophages. Furthermore, PGC-1 alpha expression reversed the miR-382-induced changes in the metabolic state of TAMs and the effects of TAMs on breast cancer cells. Of note, the in vivo growth and metastasis of 4T1 cells were inhibited by miR-382-overexpressing TAMs. Taken together, the results of the present study suggest that miR-382 may alter the metabolic status of macrophages by targeting PGC-1 alpha, thereby decreasing the proportion of TAMs with the M2 phenotype, and inhibiting the progression and metastasis of breast cancer."

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