MiR-27b suppresses epithelial-mesenchymal transition and chemoresistance in lung cancer by targeting Snail1

Life Sci. 2020 Aug 1:254:117238. doi: 10.1016/j.lfs.2019.117238. Epub 2019 Dec 28.

Abstract

Heading aims: MicroRNA-27b (miR-27b) has been shown to play a role in the progression of many different forms of cancer, but its specific relevance in the context of non-small cell lung cancer (NSCLC) remains uncertain. As such, this study sought to explore the role of miR-27b in NSCLC and the mechanisms whereby it functions.

Materials and methods: We quantified miR-27b and target gene expression via quantitative real-time PCR (RT-qPCR).We then used functional including proliferation assays, migration assay, flow cytometry, and western blotting to explore the mechanisms whereby miR-27b functions in vitro and in vivo. We additionally confirmed miR-27b target genes via luciferase reporter assay.

Key findings: We observed a marked decrease in miR-27b expression in NSCLC patient samples relative to paracancerous control tissues. We further found that altering miR-27b expression levels in vitro affected NSCLC tumor cell migration, proliferation, and ability to undergo epithelial-mesenchymal transition. Through the use of target prediction algorithms we identified Snail to be a miR-27b target protein that was suppressed when this miRNA was highlight expressed. Lastly, we found miR-27b expression to increase NSCLC cell sensitivity to cisplatin through its ability to target Snail.

Significance: Our results clearly demonstrate that miR-27b can suppress NSCLC tumor development and progression, highlighting this miR-27b/Snail1 axis as putative target for the therapeutic treatment of NSCLC.

Keywords: Chemoresistance; Lung cancer; Snail1; miR-27b.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Down-Regulation
  • Drug Resistance, Neoplasm*
  • Epithelial-Mesenchymal Transition / physiology*
  • HEK293 Cells
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • MicroRNAs / physiology*
  • Snail Family Transcription Factors / physiology*

Substances

  • Antineoplastic Agents
  • MIRN27 microRNA, human
  • MicroRNAs
  • SNAI1 protein, human
  • Snail Family Transcription Factors