Paxillin predicts survival and relapse in non-small cell lung cancer by microRNA-218 targeting

Cancer Res. 2010 Dec 15;70(24):10392-401. doi: 10.1158/0008-5472.CAN-10-2341.

Abstract

Paxillin (PXN) gene mutations are associated with lung adenocarcinoma progression and PXN is known to be a target gene of microRNA-218 (miR-218). On this basis, we hypothesized that PXN overexpression via miR-218 suppression may promote tumor progression and metastasis and that PXN may predict survival and relapse in non-small cell lung cancer (NSCLC). Expression of miR-218 and PXN in 124 surgically resected lung tumors were evaluated by real-time PCR and immunohistochemical analysis. The prognostic value of miR-218 and PXN expression on overall survival (OS) and relapse-free survival (RFS) was analyzed by the Kaplan-Meier test and Cox regression analysis. miR-218 expression in lung tumors was negatively associated with PXN expression. Multivariate analyses showed that PXN and miR-218 might independently predict OS and RFS, respectively, in NSCLC. Moreover, patients with low miR-218 combined with PXN-positive had the worst OS and RFS among the 4 combinations. In a cell model, PXN was negatively regulated by miR-218 and cell proliferation, invasion, and soft agar colony formation were enhanced by PXN overexpression induced by miR-218 suppression. Taken together, our findings suggest that PXN overexpression induced by miR-218 suppression is an independent predictor of survival and relapse in NSCLC, highlighting PXN as a potential therapeutic target to improve clinical outcomes in this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Cell Line, Tumor
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Molecular Targeted Therapy / methods
  • Neoplasm Invasiveness
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism
  • Paxillin / biosynthesis*
  • Paxillin / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Transcription, Genetic
  • Up-Regulation

Substances

  • E6 protein, Human papillomavirus type 16
  • MIRN218 microRNA, human
  • MicroRNAs
  • Oncogene Proteins, Viral
  • Paxillin
  • RNA, Messenger
  • Repressor Proteins