The depletion of PinX1 involved in the tumorigenesis of non-small cell lung cancer promotes cell proliferation via p15/cyclin D1 pathway

Molecular Cancer

Research

Mei Li¹  Dan Xie²  Xiao-Han Jin²  Wei-Juan Huang³  Jia-Xing Zhang⁴  Xiao-Peng Tian⁵ 

[1] Department of Pathology, Cancer Center, Sun Yat-Sen University, Guangzhou, China;State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China;Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China;Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China;Department of Oncology, The first Affiliated Hospital, Sun Yat-Sen University, No.58, Zhongshan Second Road, 510080, Guangzhou, China;Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China;State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China;

关键词: PinX1;    Non-small cell lung cancer;    BMP5;    Cell cycle;    P15;   

DOI  :  10.1186/s12943-017-0637-4

 received in 2016-07-26, accepted in 2017-03-13,  发布年份 2017

来源: Springer

【 摘 要 】

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 gene PinX1 homozygous 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.

【 授权许可】

CC BY   
© The Author(s). 2017