MiR-21 modulates the polarization of macrophages and increases the effects of M2 macrophages on promoting the chemoresistance of ovarian cancer

被引:71
作者
An, Yuanyuan [1 ]
Yang, Qing [1 ]
机构
[1] China Med Univ, Shengjing Hosp, Dept Gynecol & Obstet, Shenyang 110004, Liaoning, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-21; Macrophage polarization; Chemoresistance; Ovarian cancer; PROLIFERATION; METASTASIS; RESISTANCE;
D O I
10.1016/j.lfs.2019.117162
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Aims: Chemoresistance is a major underlying cause of relapse or death in ovarian cancer patients. Emerging evidence has shown that macrophages could play an essential role in mediating the chemoresistance of cancer cells. MiR-21 has been reported to be an oncogene, which promotes chemoresistance in cancer. Here, we aim to investigate the role that miR-21 plays in polarization of macrophages and ovarian cancer progression. Main methods: The CIBERSORT algorithm was used to investigate immune cell infiltration in ovarian cancer tissues. To explore the role that miR-21 played in macrophages, M2 macrophages transfected with a miR-21 mimic or a miR-21 inhibitor were co-cultured with ovarian cancer cells. Western blotting was used to detect protein expression levels. CCK8 was used to detect the IC50 of ovarian cancer cells. Flow cytometry was used to detect apoptosis and the cell cycle of ovarian cancer cells. Key findings: In this study, we found that higher expression of M1 macrophages and lower expression of M2 macrophages correlated with a better prognosis of ovarian cancer patients. M2 macrophages promoted the chemoresistance of ovarian cancer cells. The results showed that miR-21 could partially regulate the polarization of macrophages. Furthermore, M2 macrophages transfected with the miR-21 mimic significantly promoted chemoresistance and inhibited apoptosis of ovarian cancer cells, while the M2 macrophages transfected with the miR-21 inhibitor showed the opposite effects. Significance: miR-21 plays an important role in regulating macrophage polarization, therefore increasing the M2 macrophage-mediated chemoresistance in ovarian cancer cells.
引用
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页数:10
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共 36 条
[1]   Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma [J].
Arroyo, Jason D. ;
Chevillet, John R. ;
Kroh, Evan M. ;
Ruf, Ingrid K. ;
Pritchard, Colin C. ;
Gibson, Donald F. ;
Mitchell, Patrick S. ;
Bennett, Christopher F. ;
Pogosova-Agadjanyan, Era L. ;
Stirewalt, Derek L. ;
Tait, Jonathan F. ;
Tewari, Muneesh .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (12) :5003-5008
[2]   Tumor-associated stromal cells as key contributors to the tumor microenvironment [J].
Bussard, Karen M. ;
Mutkus, Lysette ;
Stumpf, Kristina ;
Gomez-Manzano, Candelaria ;
Marini, Frank C. .
BREAST CANCER RESEARCH, 2016, 18
[3]  
Chuang HY, 2019, PRECLINICAL EVIDENCE, V8
[4]   PARP Inhibitors and the Evolving Landscape of Ovarian Cancer Management: A Review [J].
Cook, Sarah A. ;
Tinker, Anna, V .
BIODRUGS, 2019, 33 (03) :255-273
[5]  
Datta Meenal, 2019, Am Soc Clin Oncol Educ Book, V39, P165, DOI 10.1200/EDBK_237987
[6]   Hypoxic non-small-cell lung cancer cell-derived exosomal miR-21 promotes resistance of normoxic cell to cisplatin [J].
Dong, Caijun ;
Liu, Xingwang ;
Wang, Huisheng ;
Li, Jutao ;
Dai, Lei ;
Li, Jun ;
Xu, Zhen .
ONCOTARGETS AND THERAPY, 2019, 12 :1947-1956
[7]   Upregulation of miR-21 in Cisplatin Resistant Ovarian Cancer via JNK-1/c-Jun Pathway [J].
Echevarria-Vargas, Ileabett M. ;
Valiyeva, Fatma ;
Vivas-Mejia, Pablo E. .
PLOS ONE, 2014, 9 (05)
[8]  
Feng Z, 1979, CLIN SCI
[9]  
Franca G.M., 2019, MACROPHAGES SUBPOPUL, V33
[10]   Detection of circulating microRNAs with Ago2 complexes to monitor the tumor dynamics of colorectal cancer patients during chemotherapy [J].
Fuji, Tomokazu ;
Umeda, Yuzo ;
Nyuya, Akihiro L. ;
Taniguchi, Fumitaka L. ;
Kawai, Takashi ;
Yasui, Kazuya ;
Toshima, Toshiaki ;
Yoshida, Kazuhiro ;
Fujiwara, Toshiyoshi ;
Goel, Ajay ;
Nagasaka, Takeshi .
INTERNATIONAL JOURNAL OF CANCER, 2019, 144 (09) :2169-2180