MicroRNA-630 may confer favorable cisplatin-based chemotherapy and clinical outcomes in non-small cell lung cancer by targeting Bcl-2.
MicroRNA-630 may confer favorable cisplatin-based chemotherapy and clinical outcomes in non-small cell lung cancer by targeting Bcl-2.
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DOI：
10.18632/oncotarget.24474
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发表时间：
2018-03-02
期刊：
影响因子：
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通讯作者：
Lee H
中科院分区：
文献类型：
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作者：
Chen MJ;Wu DW;Wang GC;Wang YC;Chen CY;Lee H
microRNA-630（miR-630）在多种人类癌症的肿瘤进展中起双重作用。然而，miR-630在非小细胞肺癌（NSCLC）化疗耐药性和预后中的作用仍有待阐明。这项回顾性研究纳入了114例手术切除的NSCLC患者，这些患者经历了肿瘤复发并接受了基于顺铂的化疗。目的是检查miR-630（及其对Bcl-2表达的靶向作用）与顺铂化疗反应之间的可能关联。肿瘤患者表达低miR-630，高Bcl-2，以及两者的组合比他们的同行更有可能表现出不利的反应顺铂为基础的化疗。Kaplan-Meier和考克斯回归分析表明，miR-630水平低、Bcl-2水平高以及二者联合可独立预测NSCLC患者的总生存期和无复发生存期。收集6种类型的NSCLC细胞，通过MTT测定法测定顺铂产生50%存活率的抑制浓度（IC 50）。除A549细胞外，在这些细胞类型中，顺铂的IC 50值与miR-630表达水平呈负相关。在机制上，低miR-630表达通过在NSCLC细胞中去靶向Bcl-2而赋予顺铂抗性和集落形成。因此，我们认为，低miR-630，高Bcl-2，以及两者的组合可能潜在地预测一个不利的化疗反应和不良的结果与NSCLC患者。
MicroRNA-630 (miR-630) plays dual roles in tumor progression in various human cancers. However, the role of miR-630 in chemoresistance and prognosis in non-small cell lung cancer (NSCLC) remains to be elucidated. This retrospective study enrolled 114 surgically resected patients with NSCLC who experienced tumor relapse and underwent cisplatin-based chemotherapy. The aim was to examine the possible association between miR-630 (and its targeting of Bcl-2 expression) and the response to cisplatin-based chemotherapy. Patients with tumors expressing low miR-630, high Bcl-2, and a combination of both were more likely than their counterparts to show unfavorable responses to cisplatin-based chemotherapy. Kaplan–Meier and Cox regression analysis indicated that low miR-630, high Bcl-2, and a combination of both may independently predict poor overall survival and short relapse-free survival in patients with NSCLC. Six types of NSCLC cells were collected to determine the inhibitory concentration of cisplatin yielding 50% viability (IC50) by the MTT assay. The IC50 value for cisplatin was negatively correlated with miR-630 expression levels among these cell types, except for A549 cells. Mechanistically, low miR-630 expression conferred cisplatin resistance and colony formation by de-targeting Bcl-2 in NSCLC cells. We therefore suggest that low miR-630, high Bcl-2, and a combination of both may potentially predict an unfavorable chemotherapeutic response and poor outcome in patients with NSCLC.