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

Mol Cancer. 2017 Apr 4;16(1):74. doi: 10.1186/s12943-017-0637-4.

Abstract

Background: The 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.

Methods: PinX1 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.

Results: More 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.

Conclusion: The cost-effective expression of PinX1 could constitute a novel molecular predictor/marker for NSCLC management.

Keywords: BMP5; Cell cycle; Non-small cell lung cancer; P15; PinX1.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers, Tumor
  • Bone Morphogenetic Protein 5 / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Cell Cycle
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism*
  • Cyclin D1 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p15 / metabolism*
  • Databases, Nucleic Acid
  • Disease Models, Animal
  • Female
  • Gene Deletion
  • Gene Silencing
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Signal Transduction*
  • Tumor Suppressor Proteins / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • BMP5 protein, human
  • Biomarkers, Tumor
  • Bone Morphogenetic Protein 5
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p15
  • PINX1 protein, human
  • Tumor Suppressor Proteins
  • Cyclin D1