The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancer
The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancer
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DOI：
10.1016/j.ygyno.2014.01.034
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发表时间：
2014-03-01
影响因子：
4.7
通讯作者：
Bourguignon, Lilly Y. W.
中科院分区：
文献类型：
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作者：
Chan, John K.;Blansit, Kevin;Bourguignon, Lilly Y. W.
背景MicroRNA与肿瘤发生、耐药性和癌症预后有关。我们研究了microRNA-21（miR-21）在调节卵巢癌耐药中的作用。我们使用亲本和顺铂耐药卵巢细胞系来证明miR-21在耐药性中的作用，并研究miR-21的基因靶点。新鲜肿瘤标本用于验证我们的体外研究结果。顺铂耐药卵巢细胞的耐药性是亲本细胞系的四倍。miR-21在microRNA微阵列上的抗性细胞系中过表达，随后用gRT-PCR验证。使用抗microRNA抑制剂，我们证明了miR-21衰减逆转了耐药细胞系和亲本细胞系中的耐药表型。基于annexin V-FITC免疫染色的miR-21诱导的细胞凋亡的抑制。使用Western blot分析，miR-21敲低增强了肿瘤抑制因子PDCD 4的表达，并减弱了凋亡抑制因子c-IAP 2的表达。使用101例来自癌症基因组图谱中的晚期卵巢癌患者的标本，我们发现肿瘤过表达miR-21的女性与较短的无进展生存期相关。我们的数据表明，miR-21通过凋亡和细胞存活途径调节耐药性。靶向miR-21可能在治疗耐药卵巢癌中具有临床实用性。爱思唯尔公司出版
Background. MicroRNAs have been implicated in tumorigenesis, drug resistance, and prognosis in cancer. We investigated the role of microRNA-21 (miR-21) in regulating ovarian cancer drug resistance.Methods. We used parental and cisplatin resistant ovarian cell lines to demonstrate the role of miR-21 in drug resistance and investigated the gene targets of miR-21. Fresh tumor specimens were used to validate our in vitro findings.Results. Cisplatin resistant ovarian cells were four-fold more resistant compared to the parental cell line. MiR-21 was overexpressed in the resistant cell line on microRNA microarray, which was subsequently validated with gRT-PCR. Using anti-microRNA inhibitors, we demonstrated that miR-21 attenuation reversed the drug resistant phenotype in both the resistant and parental cell lines. The inhibition of miR-21 induced apoptosis based on annexin V-FITC immunostaining. Using Western blot analysis, miR-21 knockdown enhanced the expression of tumor suppressor PDCD4, and attenuated apoptosis inhibitor c-IAP2. Using 101 specimens from advanced ovarian cancer patients enrolled in The Cancer Genome Atlas, we found that women with tumors that overexpressed miR-21 were associated with a shorter progression-free survival.Conclusion. Our data suggest that miR-21 regulates drug resistance via apoptosis and cellular survival pathways. Targeting miR-21 may have clinical utility in the treatment of resistant ovarian cancer. Published by Elsevier Inc.