Elevation of circular RNA circ_0003645 forecasts unfavorable prognosis and facilitates cell progression via miR-1179/TMEM14A pathway in non-small cell lung cancer

Biochem Biophys Res Commun. 2019 Apr 16;511(4):921-925. doi: 10.1016/j.bbrc.2019.03.011. Epub 2019 Mar 8.

Abstract

Background: Non-small cell lung cancer (NSCLC) is a highly aggressive malignancy with increasing incidence across the world. The role and mechanism of circular RNAs (circRNAs) in the pathogenesis of NSCLC have not been understood exactly. In this work, we aims to explore a novel NSCLC-associated circRNA, circ_0003645.

Methods: The expression profile of circ_0003645 was evaluated in NSCLC tissue specimens and cells. Additionally, the correlation between circ_0003645 and clinical features/patients' prognosis were investigated. Functionally, CCK-8, clone formation, flow cyometric and transwell assays were performed in two cell lines. Furthermore, dual-luciferase reporter and rescue experiments were carried out to elucidate the mechanism of circ_0003645.

Results: The data demonstrated an upregulation of circ_0003645 in patients' tissue specimens and cells. Overexpression of circ_0003645 in tissues was related to advanced TNM stages, positive lymph node invasion and unfavorable prognosis for the patients with NSCLC. In addition, gain and loss of function assays uncovered that circ_0003645 functioned as an oncogene in NSCLC cells. Moreover, circ_0003645 acted as a ceRNA to sponge miR-1179, which resulted in the elevation of TMEM14A expression and facilitated cell progression.

Conclusions: This study indicates that circ_0003645 might possess crucial potential as a prognosis predictor and therapeutic target for NSCLC patients.

Keywords: Circular RNA; NSCLC; TMEM14A; circ_0003645; miR-1179.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / genetics*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Membrane Proteins / genetics*
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • RNA, Circular / genetics*
  • Up-Regulation

Substances

  • Apoptosis Regulatory Proteins
  • MIRN1179 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Circular
  • TMEM14A protein, human