Role of microRNAs in drug-resistant ovarian cancer cells
Role of microRNAs in drug-resistant ovarian cancer cells
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DOI：
10.1016/j.ygyno.2008.08.017
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发表时间：
2008-12-01
影响因子：
4.7
通讯作者：
Ferlini, Cristiano
中科院分区：
文献类型：
--
作者：
Sorrentino, Antonio;Liu, Chang-Gong;Ferlini, Cristiano
目标。化疗是治疗晚期卵巢癌的首选治疗方法，但耐药性的产生会阻碍长期治疗的成功。最近的研究强调了非编码 RNA、微小 RNA (miRNA) 在癌症发展中的参与，并提出了一些关于它们可能参与耐药性进化的猜想。这项工作的目的是鉴定参与卵巢癌化疗耐药性发展的选定 microRNA。方法。使用微阵列平台评估一组紫杉醇（A2780TAX、A2780TC1 和 A2780TC3）和顺铂耐药（A2780CIS）细胞中 miRNA 谱的高通量分析，并随后使用 qPCR 和 Northern 印迹进行验证。对 miR-130a 和目标 M-CSF 进行下游目标验证。]结果。六种 miRNA（let-7e、miR-30c、miR-125b、miR-130a 和 miR-335）在所有耐药细胞系中始终以不同的方式表达。 Let-7e 在 A2780TAX 细胞中上调，而在其他耐药细胞系中下调。 miR-125b 出现相反的现象，其在 A2780TAX 中下调，而在其他细胞系中上调。 miR-30c、miR-130a 和 miR-335 在所有耐药细胞系中均下调，从而表明直接参与化疗耐药性的发生。最后，miR-130a 的下游靶点验证得到证实，其下调与 M-CSF 基因的翻译激活有关，M-CSF 基因是卵巢癌的已知耐药因子。结论。我们的结果表明，卵巢癌耐药性与独特的 miRNA 指纹相关，而 miRNA 微阵列可以作为监测化疗结果的预后工具。 (C) 2008 Elsevier Inc. 保留所有权利。
Objectives. Chemotherapy is the preferred therapeutic approach for the therapy of advanced ovarian cancer, but a successful long-term treatment is prevented by the development of drug resistance. Recent works have underlined the involvement of non-coding RNAs, microRNAs (miRNAs) in cancer development, with several conjectures regarding their possible involvement in the evolution of drug resistance. This work was aimed to identify selected microRNAs involved in the development of chemoresistance in ovarian cancer.Methods. High-throughput analysis of the miRNA profile in a panel of paclitaxel- (A2780TAX, A2780TC1 and A2780TC3) and cisplatin-resistant (A2780CIS) cells was assessed using a microarray platform and subsequent validation with qPCR and Northern blots. Downstream target validation was performed for miR-130a and the target M-CSF.]Results. Six miRNAs (let-7e, miR-30c, miR-125b, miR-130a and miR-335) were always diversely expressed in all the resistant cell lines. Let-7e was upregulated in A2780TAX cells, while it was downregulated in the other resistant cell lines. The opposite phenomenon was obtained for miR-125b, which was downregulated in A2780TAX and upregulated in the other cell lines. The miR-30c, miR-130a and miR-335 were downregulated in all the resistant cell lines, thereby suggesting a direct involvement in the development of chemoresistance. Finally downstream target validation was proven for the miR-130a, whose downregulation was linked to the translational activation of the M-CSF gene, a known resistance factor for ovarian cancer.Conclusions. Our results indicate that ovarian cancer drug resistance is associated with a distinct miRNA fingerprint, and miRNA microarrays could represent a prognostic tool to monitor the chemotherapy outcome. (C) 2008 Elsevier Inc. All rights reserved.