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.
Highlights
The telomerase/telomere interacting protein PinX1 has been suggested as a tumor suppressor
The deletion of PinX1 gene accounted for the most alterations and was visualized in six non-small cell lung cancer (NSCLC) database (Lung Adenocarcinoma – Broad, Cell 2012; TCGA, Provisional; TCGA, Nature 2014; TSP, Nature 2008; Lung Squamous Carcinoma – TCGA, Provisional; TCGA, Nature 2012) (Fig. 1a)
Our results provide a basis for the concept that decreased expression PinX1 may be important in NSCLC tumorigenesis, and might be a novel predictor for NSCLC patients
Summary
The telomerase/telomere interacting protein PinX1 has been suggested as a tumor suppressor. The clinical and biological significance of PinX1 in human non-small cell lung cancer (NSCLC) is unclear. Non-small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancer, with 5 year-survival of less than 20% [2]. It has been demonstrated that PinX1 is a major haplo-insufficient tumor suppressor gene, stemming from its correlation with chromosome instability and cancer initiation [9]. Our group recently reported that does PinX1 contribute to telomerase activity and cancer tumorigenicity but it increases the sensitivity of cancer cells to DNA damage and chemo-radiotherapy [10,11,12]. Recent studies have shown that PinX1 could suppress cell cycle progression [13,14,15,16]. PinX1 was shown to arrest cell cycle on spindle assembly checkpoint
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