LncRNA MIR4435-2HG-mediated upregulation of TGF-β1 promotes migration and proliferation of nonsmall cell lung cancer cells

Environ Toxicol. 2020 May;35(5):582-590. doi: 10.1002/tox.22893. Epub 2019 Dec 25.

Abstract

The roles of long noncoding RNAs (lncRNAs) have been shown to play critical roles in tumor progression. Here, it was identified that lncRNA MIR4435-2HG was highly expressed in lung cancer tissues, especially in nonsmall cell lung cancer (NSCLC). A consistent result was obtained in lung cancer cells. Functional experiments showed that knockdown of MIR4435-2HG reduced the proliferation and migration ability of NSCLC cells. Transcriptome-sequencing analysis indicated that TGF-β signaling was mostly enriched in NSCLC cells with MIR4435-2HG knockdown. Furthermore, MIR4435-2HG was identified as an miRNA sponge for TGF-β1 and thus activated TGF-β signaling. Additionally, re-activation of TGF-β1 rescued MIR4435-2HG knockdown-mediated inhibition on the progression of NSCLC cells. Therefore, this work indicates a novel MIR4435-2HG/TGF-β1 axis responsible for NSCLC cell progression.

Keywords: MIR4435-2HG; TGF-β1; lncRNA; miRNA; nonsmall cell lung cancer.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • RNA, Long Noncoding / blood*
  • RNA, Long Noncoding / genetics
  • Transcriptional Activation
  • Transforming Growth Factor beta1 / blood
  • Transforming Growth Factor beta1 / genetics*
  • Up-Regulation

Substances

  • MIR4435-2HG long non-coding RNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TGFB1 protein, human
  • Transforming Growth Factor beta1