MicroRNA-125b promotes tumor metastasis through targeting tumor protein 53-induced nuclear protein 1 in patients with non-small-cell lung cancer.
MicroRNA-125b promotes tumor metastasis through targeting tumor protein 53-induced nuclear protein 1 in patients with non-small-cell lung cancer.
复制标题
MicroRNA-125b通过靶向肿瘤蛋白53诱导的核蛋白1促进非小细胞肺癌患者的肿瘤转移
DOI：
10.1186/s12935-015-0233-x
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发表时间：
2015
影响因子：
5.8
通讯作者：
Ren T
中科院分区：
文献类型：
--
作者：
Li Q;Han Y;Wang C;Shan S;Wang Y;Zhang J;Ren T
肺癌，主要是非小细胞肺癌（NSCLC），是全球癌症死亡的主要原因。因此，迫切需要确定参与非小细胞肺癌转移的关键效应因子，以促进新的治疗策略的发展。在这里，我们评估了miR-125b在NSCLC细胞转移中的潜在作用。方法采用肿瘤细胞分离试剂盒从手术组织中分离非小细胞肺癌细胞。采用实时荧光定量PCR和western blot检测miR-125b和TP53INP1的表达。用核因子转染试剂盒将人miR-125b模拟物、miR-125b抑制剂、TP53INP1表达质粒和TP53INP1 siRNA转染到NSCLC细胞中。采用粘附法、浸润法及肺肿瘤转移模型检测非小细胞肺癌的转移情况。结果miR-125b在具有高转移潜力的低分化非小细胞肺癌细胞中表达显著升高。上调miR-125b可增强NSCLC细胞在体外和体内的转移潜能，下调miR-125b可降低体外和体内的转移潜能。此外，肿瘤蛋白53诱导的核蛋白1 （TP53INP1）是miR-125b参与NSCLC细胞转移的重要靶点。TP53INP1是NSCLC转移的负调控因子。肿瘤组织中TP53INP1的表达降低与miR-125b的表达呈负相关，在低分化肿瘤中显著降低，与NSCLC患者的临床分期呈负相关。结论这些发现表明miR-125b在人NSCLC细胞中通过靶向TP53INP1促进肿瘤转移，揭示了microrna在肿瘤生物学中的真实临床相关性，为NSCLC临床实践提供了新的潜在候选物。
BackgroundLung cancer, predominantly non-small-cell lung cancer (NSCLC), is the leading cause of cancer deaths worldwide. There is a great need to identify critical effectors involved in metastasis of NSCLC that will facilitate the development of new therapeutic strategies. Here we evaluated the potential role of miR-125b in the metastasis of NSCLC cells.MethodsHuman NSCLC cells were isolated from surgical tissues with Cancer Cell Isolation Kit. Expressions of miR-125b and TP53INP1 were detected with real-time PCR and western blot. Human miR-125b mimics, miR-125b inhibitor, TP53INP1 expression plasmid and TP53INP1 siRNA were transfected into NSCLC cells with nucleofector transfection kit. NSCLC metastasis was determined with adhesion assay, invasive assay and lung tumor metastasis model.ResultsThe expression of miR-125b was significantly higher in poorly differentiated NSCLC cells that are endowed with high metastatic potentials. Up-regulation of miR-125b could enhance the metastatic potential of NSCLC cells in vitro and in vivo, while down-regulation of miR-125b resulted in decreased metastatic potentials in vitro and in vivo. Further, tumor protein 53-induced nuclear protein 1 (TP53INP1) was an important target of miR-125b involved in metastasis of NSCLC cells. TP53INP1 served as a negative regulator of NSCLC metastasis. Decreased expression of TP53INP1 in tumor tissues was inversely associated with their expression of miR-125b, significantly lower in poorly differentiated tumors and inversely correlated with the clinical stages in patients with NSCLC.ConclusionsThese findings demonstrated that miR-125b promoted tumor metastasis via targeting TP53INP1 in human NSCLC cells, which uncovered a real clinical relevance of microRNAs in tumor biology, and provided novel potential candidates for NSCLC clinical practice.