MiR-153-5p promotes sensibility of colorectal cancer cells to oxaliplatin via targeting Bcl-2-mediated autophagy pathway

Biosci Biotechnol Biochem. 2020 Aug;84(8):1645-1651. doi: 10.1080/09168451.2020.1760784. Epub 2020 May 7.

Abstract

Oxaliplatin (L-OHP) is one of the effective chemotherapeutic drugs for colorectal cancer (CRC). Further investigation into the molecular mechanism of chemoresistance could improve outcomes for patients with colorectal cancer. Recently, microRNAs have been reported as a key in drug resistance of tumors. In this study, we aimed to investigate the effects of miR-153-5p in L-OHP-resistant CRC cells, and its underlying mechanism. Downregulation of miR-153-5p was observed in CRC cells, while upregulation of miR-153-5p enhances the chemosensitivity of CRC/L-OHP cells. The autophagy of CRC/L-OHP cells was markedly increased after exposure to L-OHP but abolished by the upregulation of miR-153-5p. Dual-luciferase reporter assays validated that Bcl-2 was a direct target of miR-153-5p. In conclusion, our data suggested that miR-153-5p was a mediator of cisplatin resistance in colorectal cancer by affecting Bcl-2-mediated autophagy, indicating a new therapeutic target for CRC treatment.

Keywords: Bcl-2; Colorectal cancer; L-OHP resistant; autophagy; miR-153-5p.

MeSH terms

  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Antineoplastic Agents / pharmacology*
  • Autophagy / drug effects*
  • Autophagy / genetics
  • Base Pairing
  • Base Sequence
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Oxaliplatin / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction

Substances

  • Antagomirs
  • Antineoplastic Agents
  • BCL2 protein, human
  • MIRN153 microRNA, human
  • MicroRNAs
  • Oligoribonucleotides
  • Proto-Oncogene Proteins c-bcl-2
  • Oxaliplatin