miR-1271对卵巢癌SKOV3/DDP细胞顺铂耐药的影响及其机制

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摘要目的: 研究miR-1271在卵巢癌SKOV3/DDP细胞顺铂耐药形成中的作用。方法: 采用实时定量PCR法检测卵巢癌SKOV3/DDP细胞和母代SKOV3细胞中miR1271的表达，并通过蛋白质印迹法检测上述细胞X连锁凋亡抑制蛋白(X-linked inhibitor of apoptosis protein,XIAP)的表达。构建XIAP 3′UTR荧光素酶报告质粒验证miR-1271的靶基因，在耐药细胞株中瞬时转染miR-1271模拟物以观察上调miR-1271对卵巢癌SKOV3/DDP细胞XIAP表达及顺铂耐药的影响，并运用流式细胞术检测转染miR-1271模拟物后SKOV3/DDP细胞的凋亡率。结果： miR-1271在卵巢癌SKOV3/DDP细胞中呈低表达，抗凋亡蛋白XIAP在卵巢癌SKOV3/DDP细胞中呈高表达，荧光素酶报告实验证实XIAP是直接受miR-1271调控的靶基因，在耐药株中上调miR-1271显著抑制XIAP蛋白表达水平，显著增加细胞对顺铂的敏感性，并显著增加细胞对顺铂诱导的凋亡。结论： miR-1271靶向抑制XIAP表达可增加卵巢癌SKOV3/DDP细胞对顺铂的敏感性。

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关键词 ： miR-1271, X连锁凋亡抑制蛋白, 顺铂耐药

Abstract：Objective: To investigate the possible role of miR1271 in the development of cisplatin resistance in human ovarian cancer cell line SKOV3/DDP. Methods: Using quantitative realtime PCR analysis for miRNA and Western blotting to detect the expression difference of miR1271 and Xlinked inhibitor of apoptosis protein(XIAP) between cisplatinresistant human ovarian cancer cell line SKOV3/DDP and its parental SKOV3 cell line, respectively. Constructing XIAP 3′untranslated regionbased luciferase reporter plasmids to verify the target gene of miR1271. Transient transfection of miR1271 mimic was used to upregulate the expression level of miR1271 in SKOV3/DDP cells and observe the effect of miR1271 on the expression level of XIAP and the cisplatin resistance phenotype. Flow cytometry was used to detect cisplatininduced apoptosis of SKOV3/DDP cells after the transfection. Results: miR1271 was downregulated in cisplatinresistant human ovarian cancer cell line SKOV3/DDP, which was concurrent with the overexpression of its target antiapoptotic gene XIAP in SKOV3/DDP cells, compared with the parental SKOV3 cell line. The luciferase activity of XIAP 3′untranslated regionbased reporters construct in SKOV3/DDP cells suggested that XIAP was the direct target gene of the miR1271. Overexpression of miR1271 sensitized SKOV3/DDP cells to cisplatin, inhibited the expression level of XIAP and sensitized SKOV3/DDP cells to DDPinduced apoptosis. Conclusion: miR1271 may play a role in the development of cisplatin resistance in human ovarian cancer cell line, at least in part, by modulation of apoptosis via targeting XIAP.

收稿日期: 2017-02-03

通讯作者: 陈建国（通讯作者），主任技师，硕士生导师，E-mail: cjg02@126.com

引用本文:

王广洲1, 2，秦闫燕1，卢洁1，苏兆亮1，朱伟3，陈建国4. miR-1271对卵巢癌SKOV3/DDP细胞顺铂耐药的影响及其机制[J]. 江苏大学学报:医学版, 2017, 27(02): 118-122. WANG Guang-zhou1,2, QIN Yan-yan1, LU Jie1, SU Zhao-liang1, ZHU Wei3, CHEN Jian-guo4. Effect of miR-1271 on cisplatin resistance in human ovarian cancer cell line SKOV3/DDP and its potential mechanism. Journal of Jiangsu University(Medicine Edition), 2017, 27(02): 118-122.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2017/V27/I02/118

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