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




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Molecular Cancer

, 16:74

First Online: 04 April 2017Received: 26 July 2016Accepted: 13 March 2017DOI: 10.1186-s12943-017-0637-4

Cite this article as: Tian, XP., Jin, XH., Li, M. et al. Mol Cancer 2017 16: 74. doi:10.1186-s12943-017-0637-4

Abstract

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.

KeywordsPinX1 Non-small cell lung cancer BMP5 Cell cycle P15 AbbreviationsCDK4Cyclin-dependent kinase 4

CGAThe Cancer Genome Atlas

IHCImmunohistochemistry

IPPImage pro plus

NSCLCNon-small cell lung cancer

qRT-PCRQuantitative real-time polymerase chain reaction

RbRetinoblastoma

ROCReceiver-operator curve

TRF1Telomeric repeat binding factor 1

Electronic supplementary materialThe online version of this article doi:10.1186-s12943-017-0637-4 contains supplementary material, which is available to authorized users.

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Autor: Xiao-Peng Tian - Xiao-Han Jin - Mei Li - Wei-Juan Huang - Dan Xie - Jia-Xing Zhang

Fuente: https://link.springer.com/







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