MiR-770 inhibits tumorigenesis and EMT by targeting JMJD6 and regulating WNT/β-catenin pathway in non-small cell lung cancer

Life Sci. 2017 Nov 1:188:163-171. doi: 10.1016/j.lfs.2017.09.002. Epub 2017 Sep 4.

Abstract

Aims: MicroRNAs (miRNAs) plays important role in development and disease, especially in cancer including non-small cell lung cancer (NSCLC). However, the role of miR-770 in NSCLC remains unclear. In this study, we aimed to study the function and mechanism of miR-770 in tumorigenesis of NSCLC.

Main methods: RT-qPCR was used to measure the expression levels of miR-770 in NSCLC tissues and cells. MTT assay, colony formation assay, flow cytometric analysis and transwell migration and invasion assays were performed to investigate the role of miR-770 in NSCLC cells. Bioinformatics and luciferase reporter analyses were used to demonstrate that whether the Jumonji domain-containing 6 (JMJD6) as a direct target of miR-770. The function of JMJD6 in NSCLC was also investigated. Finally, in vivo animal experiment was used to study whether miR-770 was capable of inhibiting tumor growth by inhibiting JMJD6.

Key findings: We first showed that miR-770 was downregulated in NSCLC tissues and cell lines, and the low expression of miR-770 was correlated with poor patient survival in NSCLC patients. miR-770 acted on a tumor suppressor by binding to the 3'UTR of JMJD6 and downregulated its expression in NSCLC cells. This study also demonstrated that JMJD6 played as an oncogene in NSCLC cells. miR-770 overexpression was capable of inhibiting NSCLC tumor growth by inhibiting JMJD6 and its downstream WNT/β-catenin pathway both in vitro and in vivo.

Significance: The present study indicated that miR-770 functioned as a tumor suppressor and it might be a potential biomarker and therapeutic target in NSCLC.

Keywords: JMJD6; NSCLC; WNT/β-catenin; miR-770; miRNAs.

MeSH terms

  • Apoptosis / drug effects
  • Carcinogenesis / genetics*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / biosynthesis
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • Wnt Signaling Pathway / genetics*
  • Xenograft Model Antitumor Assays
  • beta Catenin / metabolism*

Substances

  • MIRN-770 microRNA, human
  • MicroRNAs
  • beta Catenin
  • JMJD6 protein, human
  • Jumonji Domain-Containing Histone Demethylases