STAT3-induced long noncoding RNA LINC00668 promotes migration and invasion of non-small cell lung cancer via the miR-193a/KLF7 axis

Biomed Pharmacother. 2019 Aug:116:109023. doi: 10.1016/j.biopha.2019.109023. Epub 2019 May 28.

Abstract

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in non-small cell lung cancer (NSCLC) progression. Recently, a newly identified lncRNA, LncRNA LINC00668 (LINC00668), was reported to be involved in the regulation of progression of several tumors. However, the expression pattern and biological function of LINC00668 in NSCLC remains largely unclear. In this study, we found that LINC00668 expression was significantly up-regulated in both NSCLC tissues and cell lines. we also showed that LINC00668 upregulation was induced by transcription factor STAT3. Clinical investigation demonstrated that high expression level of LINC00668 was associated with advanced TNM stage, histological grade and lymph node metastasis. Moreover, multivariate analysis confirmed LINC00668 expression level to be an independent prognostic indicator for overall survival of NSCLC patients. Functional assays indicated that knockdown of LINC00668 suppressed NSCLC cells proliferation, migration and invasion, and promoted apoptosis. Mechanistic studies indicated that LINC00668 is a direct target of miR-193a, leading to down-regulation in the expression of its target gene KLF7. Our findings suggested that STAT3-induced LINC00668 contributed to NSCLC progression through upregulating KLF7 expression by sponging miR-193a, and may serve as a prognostic biomarker and a potential target for NSCLC.

Keywords: KLF7; LncRNA LINC00668; Non-small cell lung cancer; Prognosis; STAT3; miR-193a.

MeSH terms

  • 3' Untranslated Regions / genetics
  • A549 Cells
  • Apoptosis / genetics
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Proportional Hazards Models
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Regression Analysis
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Up-Regulation / genetics

Substances

  • 3' Untranslated Regions
  • KLF7 protein, human
  • Kruppel-Like Transcription Factors
  • MIRN193 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • STAT3 Transcription Factor