乳腺癌细胞LncRNA OIP5-AS1对巨噬细胞极化的影响以及极化巨噬细胞对乳腺癌细胞的反馈调节

杨恩帅; 董哲; 常鑫悦; 肖子阳; 刘洋; 郭素芬

doi:10.3971/j.issn.1000-8578.2026.25.0712

乳腺癌细胞LncRNA OIP5-AS1对巨噬细胞极化的影响以及极化巨噬细胞对乳腺癌细胞的反馈调节

Effect of LncRNA OIP5-AS1 in Breast Cancer Cells on Macrophage Polarization and Feedback Regulation of Polarized Macrophages on Breast Cancer Cells

摘要

摘要:
目的探究乳腺癌源性LncRNA OIP5-AS1经肿瘤相关巨噬细胞（TAM）M2型极化调控乳腺癌细胞迁移、侵袭及上皮—间质转化的机制。
方法 MDA-MB-231细胞分设Control组（空白对照）、NC 组（转染NC siRNA）和si-OIP5组（转染LncRNA OIP5-AS1 siRNA）。RT-qPCR检测LncRNA OIP5-AS1、IL-4和IL-13 mRNA表达；ELISA检测培养基上清IL-4和IL-13蛋白表达。Control组培养上清按不同体积比加入RPMI 1640培养基中诱导M0巨噬细胞向TAM极化，RT-qPCR检测TAM中CD206 mRNA的表达；以NC组/si-OIP5组培养基上清诱导M0型巨噬细胞，Western blot检测CD206表达；继而构建巨噬细胞MDA-MB-231共培养模型，评估MDA-MB-231细胞迁移侵袭能力并检测Vimentin、N-cadherin、E-cadherin表达变化。
结果相较于Control及NC组，si-OIP5组LncRNA OIP5-AS1表达显著下调（P<0.001），IL-13 mRNA及蛋白水平均显著降低（P<0.05），而IL-4表达在各组间无明显差异。条件培养基呈体积依赖性诱导M0巨噬细胞CD206表达，40%体积比时效应最强（P<0.001）。相较NC组，si-OIP5组CD206蛋白水平显著降低（P<0.01）。共培养体系中，si-OIP5组MDA-MB-231细胞迁移侵袭能力显著减弱（P<0.001），E-cadherin表达上调，N-cadherin及Vimentin表达下调（均P<0.01）。
结论乳腺癌源性LncRNA OIP5-AS1可经IL-13介导诱导TAM M2型极化，进而促进乳腺癌细胞的迁移、侵袭及EMT。

Abstract:
Objective To explore the mechanism by which breast cancer-derived LncRNA OIP5-AS1 regulates the migration, invasion, and epithelial-mesenchymal transition of breast cancer cells through the M2 polarization of tumor-associated macrophages (TAM).
Methods MDA-MB-231 cells were divided into the control group (blank control), the NC group (transfected with NC siRNA), and the si-OIP5 group (transfected with LncRNA OIP5-AS1 siRNA). The mRNA expression levels of LncRNAs OIP5-AS1, IL-4, and IL-13 were detected by RT-qPCR. The protein expression levels of IL-4 and IL-13 in the culture supernatant were detected by ELISA. The culture supernatant from the control group was added to RPMI 1640 medium at different volume ratios to induce the polarization of M0 macrophages into TAMs. The mRNA expression of CD206 in TAMs was detected by RT-qPCR. M0-type macrophages were induced with the medium supernatant of the NC group/si-OIP5 group, and the expression of CD206 was detected by Western blot. Subsequently, a co-culture model of macrophage and MDA-MB-231 was constructed to evaluate the migration and invasion abilities of MDA-MB-231 cells and detect the expression changes in Vimentin, N-cadherin and E-cadherin.
Results Compared with the control and NC groups, the si-OIP5 group showed significantly downregulated expression of LncRNA OIP5-AS1 (P<0.001) and significantly decreased IL-13 mRNA and protein levels (P<0.05). Meanwhile, no significant difference was observed in the expression of IL-4 among the groups. Conditioned medium induced CD206 expression in M0 macrophages in a volume-dependent manner, with the strongest effect at a 40% volume ratio (P<0.001). The CD206 protein level in the si-OIP5 group significantly decreased (P<0.01). In the co-culture system, the migration and invasion abilities of MDA-MB-231 cells in the si-OIP5 group significantly weakened (P<0.001), the expression of E-cadherin was upregulated, and the expression levels of N-cadherin and Vimentin were downregulated (both P<0.01).
Conclusion Breast cancer-derived LncRNA OIP5-AS1 can induce TAM M2 polarization mediated by IL-13, thereby promoting the migration, invasion, and EMT of breast cancer cells.

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