Involvement of miR-155/FOXO3a and miR-222/PTEN in acquired radioresistance of colorectal cancer cell line

Jpn J Radiol. 2017 Nov;35(11):664-672. doi: 10.1007/s11604-017-0679-y. Epub 2017 Sep 6.

Abstract

Purpose: Finding a novel biomarker for determining the radiosensitivity of colorectal cancer (CRC) is critical. The aim of this study is to evaluate the role of two main miRNAs including miR-222 and miR-155 in radiation response of CRC.

Materials and methods: The radioresistant CRC cell lines were established by exposing the HCT 116 cell line to fractional X-ray radiation. SubG1 fraction analysis, MTT and clonogenic assays were applied to evaluate acquired radioresistant cell line radiosensitivity. miR-222/PTEN and miR-155/FOXO3a expressions were detected by RT PCR.

Results: The clonogenic assay and sub-G1fraction analysis indicated that the RR2 sub-line was significantly more resistant than the parental cell line. MiR-222 and miR-155 were significantly upregulated in the radioresistant cell lines compared with the parental cell lines. The PTEN and FOXO3a expressions in the radioresistant cell lines were significantly higher than in the parental line.

Conclusion: These observations indicate that miR-222 and miR-155 could induce radiation resistance in colorectal cancer by targeting PTEN and FOXO3a genes, respectively. Therefore, miR-222 and miR-155 can be suggested as good biomarkers of CRC radiation response.

Keywords: Colorectal neoplasms; Radiation; Radioresistance; miR-155; miR-222.

MeSH terms

  • Cell Line, Tumor
  • Cells, Cultured
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / radiotherapy
  • Colorectal Neoplasms / genetics*
  • Forkhead Box Protein O3 / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics*
  • PTEN Phosphohydrolase / genetics*
  • Polymerase Chain Reaction
  • Radiation Tolerance / genetics*

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • MIRN155 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs
  • PTEN Phosphohydrolase
  • PTEN protein, human