miR-140-3p functions as a tumor suppressor in squamous cell lung cancer by regulating BRD9

Cancer Lett. 2019 Apr 1:446:81-89. doi: 10.1016/j.canlet.2019.01.007. Epub 2019 Jan 17.

Abstract

Squamous cell lung cancer (SqCLC) is among the most malignant lung cancers worldwide, lacking biomarkers for diagnostic and targets for treatment. In this study, we observed that miR-140-3p was expressed at low levels both in SqCLC cell lines and patient samples, while overexpression of miR-140-3p dramatically reduced the cell proliferation and invasion in SqCLC cells and Patient derived xenograft (PDX) models. Our further investigation indicated miR-140-3p negatively affected the tumorigenesis of SqCLC by down-regulating the expression of BRD9, an oncogene in SqCLC. Inhibition of BRD9 repressed SqCLC tumorigenesis by regulating c-myc expression. Meanwhile, BRD9 expression is up-regulated and negatively correlated with miR-140-3p in clinical samples; a meta-analysis of survival data indicates that SqCLC patients with high levels of BRD9 in their tumors have a worse prognosis. Collectively, our study suggests the prognostic and therapeutic roles of miR-140-3p and BRD9 axis in squamous cell lung cancer.

Keywords: Bromodomain-containing protein; Patient-derived xenograft; Tumorigenesis; c-myc; microRNA.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Mice, Inbred NOD
  • Mice, SCID
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Burden
  • Tumor Cells, Cultured

Substances

  • BRD9 protein, human
  • MYC protein, human
  • MicroRNAs
  • Mirn140 microRNA, human
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors