Overexpression of the long noncoding RNA TRHDE-AS1 inhibits the progression of lung cancer via the miRNA-103/KLF4 axis

J Cell Biochem. 2019 Oct;120(10):17616-17624. doi: 10.1002/jcb.29029. Epub 2019 May 22.

Abstract

Aim: The aim of this study was to explore the role and molecular basis of the long noncoding RNA (lncRNA) TRHDE-AS1 in lung cancer.

Methods: We used real-time polymerase chain reaction to analyze the messenger RNA expression levels of TRHDE-AS1, miR-103, and KLF4. The cell viability, proliferation, and invasion rates were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Cell Counting Kit-8, and Transwell assays to elucidate the role of TRHDE-AS1.

Results: Our results demonstrated that the lncRNA TRHDE-AS1 is mainly located in the cytoplasm and that the cell proliferation and invasion were suppressed in the group of overexpressed TRHDE-AS1. We also showed that miR-103 could directly bind to TRHDE-AS1 and provided evidence of the oncogenic function of miR-103. Besides, we proved that miR-103 exerted its function by adjusting the expression level of the tumor-suppressor gene KLF4, and the expression level was negatively associated with miR-103.

Conclusion: In summary, we determined that the effects of TRHDE-AS1 on proliferation, invasion, and cell death could be rescued by the overexpression of miR-103. Our experiments demonstrate that the TRHDE-AS1/miR-103/KLF4 axis may provide new evidence for understanding the molecular basis of lung cancer.

Keywords: KLF4; TRHDE-AS1; lung cancer; miR-103.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Apoptosis / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / genetics
  • Xenograft Model Antitumor Assays

Substances

  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • MIRN103 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding