The depletion of PinX1 involved in the tumorigenesis of non-small cell lung cancer promotes cell proliferation via p15/cyclin D1 pathway.
The depletion of PinX1 involved in the tumorigenesis of non-small cell lung cancer promotes cell proliferation via p15/cyclin D1 pathway.
复制标题
参与非小细胞肺癌肿瘤发生的 PinX1 的缺失通过 p15/cyclin D1 途径促进细胞增殖
DOI：
10.1186/s12943-017-0637-4
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发表时间：
2017-04-04
期刊：
影响因子：
37.3
通讯作者：
Zhang JX
中科院分区：
文献类型：
--
作者：
Tian XP;Jin XH;Li M;Huang WJ;Xie D;Zhang JX
背景端粒酶/端粒相互作用蛋白PinX 1被认为是一种肿瘤抑制因子。方法收集cBioportal网络资源和两组非小细胞肺癌（NSCLC）标本，分析PinX 1基因表达模式及其与NSCLC患者生存期的关系。一系列的在体内和体外试验进行阐明PinX 1对NSCLC细胞增殖的功能和潜在的mechanism.ResultsMore频率的基因PinX 1纯合缺失和杂合缺陷是第一次检索cBioportal Web资源。PinX 1的低表达与吸烟状况、组织学类型、T分期、N分期、M分期和TNM分期相关，并且是NSCLC患者学习队列（n= 93）和验证队列（n= 51）中总生存期的独立预测因子。此外，PinX 1的敲低显著加速NSCLC细胞增殖和G1/S转换，而PinX 1的异位过表达在体外和体内显著抑制细胞活力和细胞周期转换。p15/cyclin D1通路和BMP 5可能参与PinX 1相关的细胞增殖和细胞周期转换。
BackgroundThe telomerase/telomere interacting protein PinX1 has been suggested as a tumor suppressor. However, the clinical and biological significance of PinX1 in human non-small cell lung cancer (NSCLC) is unclear.MethodsPinX1 gene/expression pattern and its association with NSCLC patient survival were analyzed in cBioportal Web resource and two cohorts of NSCLC samples. A series of in vivo and in vitro assays were performed to elucidate the function of PinX1 on NSCLC cells proliferation and underlying mechanisms.ResultsMore frequency of genePinX1homozygous deletion and heterozygote deficiency was first retrieved from cBioportal Web resource. Low expression of PinX1 correlated with smoking condition, histological type, T stage, N stage, M stage and TNM stage, and was an independent predictor for overall survival in a learning cohort (n= 93) and a validation cohort (n= 51) of NSCLC patients. Furthermore, knockdown of PinX1 dramatically accelerated NSCLC cell proliferation and G1/S transition, whereas ectopic overexpression of PinX1 substantially inhibited cell viability and cell cycle transition in vitro and in vivo. p15/cyclin D1 pathway and BMP5 might contribute to PinX1-associated cell proliferation and cell cycle transition.ConclusionThe cost-effective expression of PinX1 could constitute a novel molecular predictor/marker for NSCLC management.