Up-regulation of miR-146a increases the sensitivity of non-small cell lung cancer to DDP by downregulating cyclin J.
Up-regulation of miR-146a increases the sensitivity of non-small cell lung cancer to DDP by downregulating cyclin J.
复制标题
miR-146a上调通过下调cyclin J增加非小细胞肺癌对DDP的敏感性
DOI：
10.1186/s12885-017-3132-9
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发表时间：
2017-02-15
期刊：
影响因子：
3.8
通讯作者：
Ke B
中科院分区：
文献类型：
--
作者：
Shi L;Xu Z;Wu G;Chen X;Huang Y;Wang Y;Jiang W;Ke B
研究背景以顺铂（DDP）为基础的化疗是目前肺癌常用的一线治疗方案。然而，它们的功效通常受到原发性耐药性和/或获得性耐药性的限制。本研究旨在探讨miRNA-146 a（miR-146 a）在非小细胞肺癌（NSCLC）顺铂耐药中的作用及其机制。CCK-8法检测细胞对顺铂的敏感性，流式细胞仪检测细胞凋亡，Hoechst染色法检测细胞周期，细胞侵袭/迁移实验检测细胞迁移率。结果与NC组相比，miR-146 a过表达和/或CCNJ敲低均能显著增加A549/DDP和SPC-A1/DDP细胞对DDP的敏感性，其作用机制可能是通过阻滞细胞周期、促进细胞凋亡、抑制细胞活力和运动能力。结论miR-146 a在NSCLC细胞获得性耐药中起重要作用。对miR-146 a介导的串扰网络的进一步了解可能会促进miR-146 a类似物在NSCLC治疗中的临床应用。
BackgroundCisplatin (DDP)-based chemotherapy is the common first-line therapy for lung cancer. However, their efficacy is often limited by primary drug resistance and/or acquired drug resistance. The aim of this study was to investigate the function of miRNA-146a (miR-146a) in DDP-resistant non-small cell lung cancer (NSCLC), as well as the underlying mechanisms.MethodsThe effect of overexpression of miR-146a and/or knockdown of cyclin J (CCNJ) in A549/DDP and SPC-A1/DDP cells were investigated as follows. The cellular sensitivity to DDP, cell apoptosis, cell cycle and cell mobility were detected by CCK-8, flow cytometry, hoechst staining and cell invasion/migration assay, respectively. The effects of miR-146a overexpression in NSCLC resistant cells were further analyzed in a nude mouse xenograft model.ResultsOverexpression of miR-146a and/or knockdown of CCNJ significantly increased the sensitivity to DDP in A549/DDP and SPC-A1/DDP cells compared to NC group via arresting cell cycle, enhancing cell apoptosis, inhibiting cell viability and motility in vitro and in vivo. Furthermore, miR-146a could specially degrade the mRNA of CCNJ, as examined by dual luciferase report assay.ConclusionThe study indicates a crucial role of miR-146a in the development of acquired drug resistance to DDP in NSCLC cells. Further understanding of miR-146a mediated crosstalk networks may promote the clinical use of miR-146a analogue in NSCLC therapy.