miR-129-5p通过HMGB1 调控乳腺癌MCF-7 细胞对紫杉醇的敏感性

目的：探讨miR-129-5p 通过调控高迁移率族蛋白B1 基因（high mobility group box 1，HMGB1）影响乳腺癌MCF-7 细胞对紫杉醇（paclitaxel，PTX）的敏感性。方法：采用脂质体转染技术将miR-129-5p mimics、HMGB1 小干扰RNA（si-HMGB1）分别转染入MCF-7 细胞，用PTX刺激培养细胞后，用实时荧光定量PCR检测转染后MCF-7 细胞miR-129-5p 和HMGB1 mRNA的表达，Western blotting 检测转染后MCF-7 细胞HMGB1 蛋白的表达，CCK-8 增殖实验检测转染后PTX对MCF-7 细胞增殖的影响，流式细胞术检测转染后对PTX诱导MCF-7 细胞凋亡的影响。结果：转染miR-129-5p mimics 后，MCF-7 细胞中miR-129-5p 的表达水平明显高于阴性对照组细胞（P<0.01）；过表达miR-129-5p 后可明显增强PTX抑制MCF-7 细胞的增殖和诱导细胞凋亡的能力（均P<0.05），并显著抑制HMGB1 mRNA和蛋白的表达（均P<0.05）。转染si-HMGB1 后，显著降低MCF-7 细胞HMGB1 mRNA 和蛋白的表达（均P<0.05）；干扰HMGB1 表达进一步促进PTX抑制MCF-7 细胞的增殖并诱导细胞凋亡（均P<0.05）。结论：miR-129-5p 通过下调HMGB1 的表达增强乳腺癌MCF-7 细胞对PTX的敏感性。

MiR-129-5p influences the sensitivity of breast cancer MCF-7 cells to paclitaxel by regulating HMGB1

Objective: To investigate the effect of miR-129-5p on the sensitivity of breast cancer MCF-7 cells to paclitaxel (PTX) by regulating high mobility group box 1 (HMGB1). Methods: MCF-7 cells were transfected with miR-129-5p mimics or si-HMGB1 by liposomes transfection technology before stimulated with PTX, respectively. Then, the mRNA expressions of HMGB1 and miR-129-5p in MCF-7 cells were detected by Real-time fluorescence quantitative PCR. Assessment of the expression of HMGB1 protein in MCF-7 cells was performed using Western blotting, and the effect of PTX on the proliferation of MCF-7 cells was performed by CCK-8 assay.Finally, the effect of transfection on PTX-induced apoptosis of MCF-7 cells was detected by flow cytometry. Results: After being transfected with miR-129-5p mimics, the expression of miR-129-5p was significantly higher than that of the negative control group (P<0.01). Over-expression of miR-129-5p significantly enhanced the inhibition of MCF-7 cells proliferation by PTX (P< 0.05) and PTX-induced apoptosis (P<0.05), meanwhile it also significantly inhibited the xpression of HMGB1 mRNA and protein (all P<0.05). Transfection with si-HMGB1 significantly reduced the expression of HMGB1 mRNA and protein (all P<0.05) in MCF-7 cells. HMGB1 interference further promoted PTX-induced proliferation inhibition and apoptosis of MCF-7 cells (all P<0.05). Conclusion: miR-129-5p enhanced the sensitivity of MCF-7 cells to PTX by down-regulating HMGB1.