<em>miR</em>-17-92 cluster increases the migration and invasion abilities of DU145 prostate cancer cells and enhances the cisplatin resistance

陈　昊; 周　鹏; 徐晶晶

doi:10.19401/j.cnki.1007-3639.2017.02.003

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miR-17-92 cluster increases the migration and invasion abilities of DU145 prostate cancer cells and enhances the cisplatin resistance

更新时间：2025-12-31

- miR-17-92 cluster increases the migration and invasion abilities of DU145 prostate cancer cells and enhances the cisplatin resistance
- China Oncology Vol. 27, Issue 2, Pages: 95-101(2017)
- 作者机构：
  
  苏州大学附属第一医院中心实验室,江苏,苏州,215007
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2017.02.003
  CLC：
- Published Online：22 March 2017，
  
  Published：22 March 2017
- 稿件说明：
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陈　昊,周　鹏,徐晶晶,等.

陈　昊, 周　鹏, 徐晶晶. miR-17-92 cluster increases the migration and invasion abilities of DU145 prostate cancer cells and enhances the cisplatin resistance[J]. China Oncology, 2017, 27(2): 95-101.
陈　昊,周　鹏,徐晶晶,等. DOI： 10.19401/j.cnki.1007-3639.2017.02.003.

陈　昊, 周　鹏, 徐晶晶. miR-17-92 cluster increases the migration and invasion abilities of DU145 prostate cancer cells and enhances the cisplatin resistance[J]. China Oncology, 2017, 27(2): 95-101. DOI： 10.19401/j.cnki.1007-3639.2017.02.003.

摘要

背景与目的：miR-17-92基因簇与多种疾病的发生密切相关，其在肺癌、肝癌、胃癌和前列腺癌等多种肿瘤细胞中均高表达。本研究利用慢病毒包装系统建立稳定高表达miR-17-92基因簇的DU145细胞株，探讨miR-17-92基因簇对前列腺癌DU145细胞的迁移、侵袭能力及对顺铂耐药性的影响。方法：构建高表达miR-17-92基因簇的表达载体，转染DU145细胞株，同时转染空载体作为对照，并用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction，RTFQ-PCR)进行鉴定。用xCELLigence系统监测细胞的迁移、侵袭能力及顺铂处理后的生长情况；通过划痕实验观察细胞的迁移情况；采用蛋白［质］印迹法(Western blot)、凝胶酶谱实验和RTFQ-PCR检测相关蛋白质和基因的表达以探讨miR-17-92增强DU145细胞的迁移、侵袭能力及对顺铂耐药性的相关机制。结果：DU145-miR-17-92细胞迁移速率和侵袭能力高于DU145-control细胞(P0.01)。DU145-miR-17-92细胞中整合素β1的蛋白质表达水平和基质金属蛋白酶-9(matrix metalloprotein-9，MMP-9)的活性显著高于DU145-control细胞。顺铂处理后，DU145-miR-17-92细胞的生长速度自12 h起快于DU145-control细胞并呈顺铂耐药性(P0.01)。细胞外调节蛋白激酶1/2(extracellular regulated protein kinases，ERK1/2)在DU145-miR-17-92细胞中呈现持续高水平磷酸化，顺铂处理后，其磷酸化水平无明显变化。DU145-miR-17-92细胞中切除修复互补交叉基因1(excision repair cross complementing1，ERCC1)的mRNA和蛋白质表达水平显著高于DU145-control细胞。结论：高表达miR-17-92增强了DU145细胞的迁移、侵袭能力，其机制与整合素β1的表达上调及MMP-9活性增强有关。此外，高表达miR-17-92增强了DU145细胞对顺铂的耐药性，该过程与ERK1/2的磷酸化水平增加和ERCC1的表达水平上调相关。

Abstract

Background and purpose: miR-17-92 gene cluster overexpression has been observed in various cancers

such as lung cancer

liver cancer

gastric cancer and prostate cancer. In this study

we established the stable cell line overexpressing miR-17-92 to explore the influence of miR-17-92 on the migration

invasion abilities and cisplatin resistance of the prostate cancer DU145 cells. Methods: miR-17-92 overexpression vectors were constructed. DU145 cells were infected with the viral supernatants produced by Phoenix A packaging system. Real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) was conducted to detect the expression level of miR-17-92 in the cells. The migration and invasion abilities were measured by a real-time xCELLigence system. The scratch healing assay was carried out to investigate the migration abilities. The expression of integrin β1 was detected by Western blot

and the activities of matrix metalloprotein-2 (MMP-2) and matrix metalloprotein-9 (MMP-9) were measured by gelatin zymography experiment. The cell growth of the two cell lines after the treatment of cisplatin was detected by a real-time xCELLigence system. The mRNA expression of ERCC1 was measured by RTFQ-PCR. Western blot was conducted to investigate the protein expressions of ERCC1

ERK1/2 and pERK1/2. Results: DU145-miR-17-92 cells migrated faster than DU145-control cells during the 24 h continuous monitoring (P0.01). The scratch healing assay indicated that DU145-miR-17-92 cells migrated from the edge towards the scratch center faster than DU145-control cells. DU145-miR-17-92 cells invaded through matrigel markedly faster than DU145-control cells (P0.01). The protein expression level of integrin β1 and the MMP-9 activities in DU145-miR-17-92 cells were increased than those in DU145-control cells. After the treatment of cisplatin

DU145-miR-17-92 cells grew faster than DU145-control cells

presenting cisplatin resistance (P0.01). The phosphorylation of ERK1/2 in DU145-miR-17-92 cells was constantly at a high level regardless of the treatment of cisplatin. Compared with DU145-control cells

the expression of drug resistance-related gene ERCC1 was dramatically increased in DU145-miR-17-92 cells after the treatment of cisplatin. Conclusion: miR-17- 92 overexpression increases the migration and invasion abilities of the prostate cancer DU145 cells

which is associated with the upregulated expression of integrin β1 and the increased activity of MMP-9. Besides

miR-17-92 overexpression enhances the cisplatin resistance of DU145

which is correlated with the increased phosphorylation level of ERK and the upregulated expression of ERCC1 at both the mRNA and protein levels.

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miR-17-92 cluster increases the migration and invasion abilities of DU145 prostate cancer cells and enhances the cisplatin resistance

DOI：10.19401/j.cnki.1007-3639.2017.02.003

摘要

Abstract

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