MiR-483-3p regulates oxaliplatin resistance by targeting FAM171B in human colorectal cancer cells

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):725-736. doi: 10.1080/21691401.2019.1569530.

Abstract

Oxaliplatin resistance limits the efficiency of treatment for colorectal cancer (CRC). Studies have shown that abnormal expression of microRNAs (miRNAs) were associated with tumorigenesis, cancer development and chemoresistance. The purpose of this study was to identify potential miRNAs related to oxaliplatin resistance in CRC cells. In this work, using small RNA sequencing (small RNA-Seq) and transcriptome sequencing (RNA-Seq), we found that down-regulated miR-483-3p was concurrent with up-regulated FAM171B in oxaliplatin-resistant colorectal cancer cell line HCT116/L as compared with its parental cell line HCT116. Transient transfection of miR-483-3p mimics markedly decreased the levels of FAM171B and restored oxaliplatin responsiveness of HCT116/L cells, and this alteration enhanced cell apoptosis and weakened cell migration. Whereas miR-483-3p inhibitor dramatically promoted the expression of FAM171B and enhanced oxaliplatin resistance of HCT116 cells by repressing cell apoptosis. Furthermore, knockdown of FAM171B in HCT116/L cells could also sensitize its reaction of the treatment with oxaliplatin, which was verified by the reduced cell migration. These findings demonstrate that FAM171B is a functional target of miR-483-3p in the regulation of oxaliplatin resistance in human CRC cells.

Keywords: Colorectal cancer; FAM171B; chemoresistance; miR-483-3p; oxaliplatin.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HCT116 Cells
  • Humans
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / genetics
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Oxaliplatin / pharmacology*

Substances

  • Antineoplastic Agents
  • FAM171B protein, human
  • MIRN483 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Neoplasm Proteins
  • Oxaliplatin