• Yun-Xiao Zhou, Wei Zhao, Li-Wei Mao, Yan-Li Wang, Li-Qun Xia, Min Cao, Jie Shen, and Jun Chen.
• Department of Gynaecology, The First Affiliated Hospital of Zhejiang University Medical College, Hangzhou 310003, Zhejiang, China.
• Int. J. Biochem. Cell Biol. 2018 Nov 1; 104: 25-33.

AbstractAccumulating evidence suggested that tumor-associated macrophages played crucial roles in the progression of endometrial cancer. The aim of this study was to determine the role of lncRNA NIFK-AS1 in M2-like polarization of macrophages and further to investigate the effect of NIFK-AS1 modulating macrophage polarization on the proliferation, migration and invasion of endometrial cancer cells. Human peripheral blood mononuclear cells and tumor-associated macrophages were isolated from healthy volunteers and endometrial cancer patients, respectively. The expression of NIFK-AS1 and miR-146a were detected by qRT-PCR in tumor-associated macrophages or THP-1 monocytes differentiated macrophages. The expression of NIFK-AS1 and miR-146a were decreased and increased in tumor-associated macrophages of endometrial cancer patients, respectively. NIFK-AS1 overexpression suppressed the IL-4-induced M2 polarization of THP-1 macrophages. Moreover, we found that NIFK-AS1 overexpression inhibited the 17β-estradiol-induced proliferation, migration and invasion of endometrial cancer cells through suppressing M2-like polarization of macrophages. NIFK-AS1 could interact with miR-146a and increased the expression of Notch1 through downregulating miR-146a. Further experiments revealed that miR-146a overexpression attenuated the effect of NIFK-AS1 on suppressing the M2 polarization of macrophages and the estrogen-induced proliferation, migration and invasion of endometrial cancer cells. These findings indicated that NIFK-AS1 inhibited the M2-like polarization of macrophages via targeting miR-146a, thereby reducing the estrogen-induced proliferation, migration and invasion of endometrial cancer cells. Our study highlights the important role of NIFK-AS1 in regulating the polarization and function of tumor-associated macrophages in endometrial cancer and provides novel insight into the TAMs-mediated progression of endometrial cancer.Copyright © 2018 Elsevier Ltd. All rights reserved.

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