Department of Gynaecology, The First Affiliated Hospital of Zhejiang University Medical College, Hangzhou 310003, Zhejiang, China.
Department of Obstetrics and Gynaecology, Jingning County People's Hospital, Lishui 323000, Zhejiang, China.
Int J Biochem Cell Biol. 2018 Nov;104:25-33. doi: 10.1016/j.biocel.2018.08.017. Epub 2018 Aug 31.
Accumulating 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.
越来越多的证据表明，肿瘤相关巨噬细胞在子宫内膜癌的进展中发挥着关键作用。本研究旨在确定 lncRNA NIFK-AS1 在巨噬细胞 M2 样极化中的作用，并进一步研究 NIFK-AS1 调节巨噬细胞极化对子宫内膜癌细胞增殖、迁移和侵袭的影响。分别从健康志愿者和子宫内膜癌患者中分离外周血单核细胞和肿瘤相关巨噬细胞。采用 qRT-PCR 检测肿瘤相关巨噬细胞或 THP-1 单核细胞分化的巨噬细胞中 NIFK-AS1 和 miR-146a 的表达。子宫内膜癌患者肿瘤相关巨噬细胞中 NIFK-AS1 的表达降低，miR-146a 的表达增加。NIFK-AS1 过表达抑制 THP-1 巨噬细胞中 IL-4 诱导的 M2 极化。此外，我们发现 NIFK-AS1 过表达通过抑制巨噬细胞 M2 样极化抑制 17β-雌二醇诱导的子宫内膜癌细胞增殖、迁移和侵袭。NIFK-AS1 可以与 miR-146a 相互作用，并通过下调 miR-146a 增加 Notch1 的表达。进一步的实验表明，miR-146a 过表达减弱了 NIFK-AS1 抑制巨噬细胞 M2 极化和雌激素诱导的子宫内膜癌细胞增殖、迁移和侵袭的作用。这些发现表明，NIFK-AS1 通过靶向 miR-146a 抑制巨噬细胞 M2 样极化，从而减少雌激素诱导的子宫内膜癌细胞增殖、迁移和侵袭。本研究强调了 NIFK-AS1 在调节子宫内膜癌肿瘤相关巨噬细胞极化和功能中的重要作用，并为 TAMs 介导的子宫内膜癌进展提供了新的见解。
