Associations of deregulation of mir-365 and its target mRNA TTF-1 and survival in patients with NSCLC

Int J Clin Exp Pathol. 2015 Mar 1;8(3):2392-9. eCollection 2015.

Abstract

microRNA (mir)-365 exerts tumor suppressor function by targeting thyroid transcription factor-1 (TTF-1) in lung cancer cells. The purpose of the present study was to assess mir-365 and its target mRNA TTF-1 in lung cancer and their correlations with patients' survival. Quantitative real-time PCR was used to examine the expression levels of mir-365 and TTF-1 in tumor tissue and its adjacent noncancerous tissue of 126 patients with non-small cell lung cancer (NSCLC). Our results showed that mir-365 was significantly decreased in tumor tissue than that in normal tissue (P=0.006), however, TTF-1 was significantly increased in tumor tissue than in normal tissue (P<0.001). Besides, significant correlations between decreased mir-365 and advanced tumor-node-metastasis (TNM) stage (P=0.001) and regional lymph node involvement (P=0.037) was observed. The similar result was also found between increased TTF-1 and TNM stage (P=0.003). Furthermore, mir-365 downregulation or TTF-1 upregulation were associated with poor outcome of patients than mir-365 upregulation or TTF-1 downregulation (for mir-365: P<0.001; for TTF-1: P=0.002). Of note, combination of decreased mir-365 and increased TTF-1 had worst overall survival (P<0.001). In conclusion, aberrant expression of mir-365/TTF-1 may be involved in the tumor development in patients with NSCLC. Moreover, mir-365 and TTF-1 could jointly predict the prognosis of patients and their combination may serve as a biomarker to predict risk of poor survival in NSCLC patients. Mir-365/TTF-1 might serve as a potential therapeutic target for clinical treatment of NSCLC.

Keywords: NKX2-1; microRNA-365; non-small cell lung cancer; outcome; prognostic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Thyroid Nuclear Factor 1
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • MIRN365 microRNA, human
  • MicroRNAs
  • NKX2-1 protein, human
  • Nuclear Proteins
  • RNA, Messenger
  • Thyroid Nuclear Factor 1
  • Transcription Factors