MicroRNA-34c-3p target inhibiting NOTCH1 suppresses chemosensitivity and metastasis of non-small cell lung cancer

J Int Med Res. 2020 Mar;48(3):300060520904847. doi: 10.1177/0300060520904847.

Abstract

Background: Chemotherapy is the standard treatment for non-small cell lung cancer (NSCLC). However, chemoresistance frequently occurs, making the treatment of NSCLC more difficult.

Method: We combined clinical and experimental studies to establish the role of microRNA (miR)-34c in NSCLC metastasis and chemoresistance.

Results: MiR-34c expression was significantly decreased in patients with NSCLC who showed a poor chemoresponse and metastasis. Overexpression of miR-34c sensitized NSCLC cells to paclitaxel and cisplatin both in vitro and in vivo. Furthermore, we found that NOTCH1 was target of miR-34c in NSCLC cells and played a key role in the effects of miR-34c on NSCLC.

Conclusion: NSCLC metastasis and chemoresistance are suppressed though the miR-34c/NOTCH1 axis. MiR-34c has important implications in the development of therapeutic strategies for metastasis and chemoresistance in NSCLC.

Keywords: NOTCH1; Non-small cell lung cancer; chemoresistance; gene expression; metastasis; miR-34c.

MeSH terms

  • Animals
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Metastasis
  • Receptor, Notch1 / metabolism*

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • NOTCH1 protein, human
  • Receptor, Notch1