miRNA-132通过靶向PDCD4在多发性骨髓瘤细胞黏附介导的耐药性中的作用

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摘要目的探讨miR-132对程序性死亡4基因（PDCD4）的靶向作用，及其在多发性骨髓瘤细胞黏附介导的耐药性中的作用。方法利用荧光素酶报告基因分析miR-132对PDCD4的靶向调控关系。对人骨髓瘤细胞株U266进行miR模拟物和抑制物转染，之后比较地塞米松（Dex）、多柔比星（Dox）、硼替佐米（Bort）处理下U266细胞的药物敏感性。Transwell法检测U266细胞的迁移能力。MTT法和CCK-8法检测细胞增殖活性。结果 Dex和Dox干预后细胞的抑制率显著上升（P ＜ 0.05），而Bort干预后细胞的抑制率无显著变化（P > 0.05）。荧光素酶报告基因分析结果证实PDCD4是miR-132的靶基因。上调miR-132可以抑制PDCD4基因和和蛋白的表达（P ＜ 0.05）。miR-132上调后U266细胞的迁移距离显著增加（P ＜ 0.05）。miR-132上调后U266细胞的黏附率和增殖活性显著增加（P ＜ 0.05）。结论 miR-132可以靶向PDCD4调控多发性骨髓瘤细胞黏附介导的耐药性。

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	周佳妮1 马泳泳2

关键词 ： miR-132, 程序性死亡4基因, 多发性骨髓瘤, 耐药性, 细胞黏附

Abstract：Objective To explore the targeting effect of miR-132 on programmed death 4 gene (PDCD4) and its role in the adhesion mediated drug resistance of multiple myeloma cells. Methods Luciferase reporter gene was used to analyze the targeting regulation of miR-132 on PDCD4. Human myeloma cell line U266 was transfected with miR mimic and inhibitor, and then the drug sensitivity of U266 cells treated with Dexamethasone (Dex), Doxorubicin (Dox) and Bortezomib (Bort) was compared. Transwell method was used to detect the migration ability of U266 cells. MTT and CCK-8 methods were used to detect cell proliferation. Results After Dex and Dox intervention, the inhibition rate of cells increased significantly (P < 0.05), while the inhibition rate of Bort did not change significantly (P > 0.05). Luciferase reporter gene analysis confirmed that PDCD4 was the target gene of miR-132. Up regulation of miR-132 could inhibit the expression of PDCD4 gene and protein (P < 0.05). The migration distance of U266 cells increased (P < 0.05). After miR-132 was up-regulated, the adhesion rate and proliferation activity of U266 cells increased (P < 0.05). Conclusion miR-132 can target PDCD4 to regulate multiple myeloma cell adhesion mediated drug resistance.

Key words： miR-132 Programmed death 4 gene Multiple myeloma Drug resistance Cell adhesion

基金资助:国家自然科学基金青年科学基金项目（816001 67）。

引用本文:

周佳妮1 马泳泳2. miRNA-132通过靶向PDCD4在多发性骨髓瘤细胞黏附介导的耐药性中的作用[J]. 中国医药导报, 2020, 17(14): 4-7,13.
ZHOU Jia′ni1 MA Yongyong2. The role of miRNA-132 in multiple myeloma cell adhesion mediated drug resistance by targeting PDCD4. 中国医药导报, 2020, 17(14): 4-7,13.

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