Open Access

miR‑361 enhances sensitivity to 5‑fluorouracil by targeting the FOXM1‑ABCC5/10 signaling pathway in colorectal cancer

  • Authors:
    • Luyao Zhang
    • Bo Li
    • Beilin Zhang
    • Hua Zhang
    • Jian Suo
  • View Affiliations

  • Published online on: August 14, 2019     https://doi.org/10.3892/ol.2019.10741
  • Pages: 4064-4073
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is one of most common malignancies worldwide. 5‑fluorouracil (5‑FU) is a mainstay of CRC treatment, particularly in patients with advanced stages of the disease; however, 5‑FU‑based chemotherapy is not always effective and may result in progression of the disease. The present study investigated several candidate microRNAs (miRs) in parental and 5‑FU‑resistant HCT116 and HT29 cells, and identified miR‑361 as a novel regulator of chemosensitivity. Overexpression of miR‑361 enhanced the 5‑FU susceptibility of parental and resistant HCT116 and HT29 cells in vitro. Impaired colony formation capacity and increased cell apoptosis (as determined via flow cytometry) was observed in resistant HCT116 and HT29 cells. Furthermore, forkhead box M1 (FOXM1) was identified as a target gene of miR‑361 using a dual‑luciferase reporter assay, western blotting and reverse transcription‑quantitative PCR. Additionally, FOXM1 knockdown improved the cytotoxicity of 5‑FU in resistant CRC. ATP binding cassette subfamily C members 5 and 10 (ABCC5/10) were found to be downstream effectors of miR‑361. In conclusion, miR‑361 increased chemosensitivity, at least in part, via modulation of FOXM1‑ABCC5/10. miR‑361 may serve as a potential therapeutic target for patients with CRC.

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October 2019
Volume 18 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
APA
Zhang, L., Li, B., Zhang, B., Zhang, H., & Suo, J. (2019). miR‑361 enhances sensitivity to 5‑fluorouracil by targeting the FOXM1‑ABCC5/10 signaling pathway in colorectal cancer . Oncology Letters, 18, 4064-4073. https://doi.org/10.3892/ol.2019.10741
MLA
Zhang, L., Li, B., Zhang, B., Zhang, H., Suo, J."miR‑361 enhances sensitivity to 5‑fluorouracil by targeting the FOXM1‑ABCC5/10 signaling pathway in colorectal cancer ". Oncology Letters 18.4 (2019): 4064-4073.
Chicago
Zhang, L., Li, B., Zhang, B., Zhang, H., Suo, J."miR‑361 enhances sensitivity to 5‑fluorouracil by targeting the FOXM1‑ABCC5/10 signaling pathway in colorectal cancer ". Oncology Letters 18, no. 4 (2019): 4064-4073. https://doi.org/10.3892/ol.2019.10741