Open Access

p53 expression confers sensitivity to 5‑fluorouracil via distinct chromatin accessibility dynamics in human colorectal cancer

  • Authors:
    • Chul Min Yang
    • Moo-Koo Kang
    • Woong-Jae Jung
    • Jung-Sik Joo
    • Yong-Jin Kim
    • Yeeun Choi
    • Hyoung-Pyo Kim
  • View Affiliations

  • Published online on: January 24, 2021     https://doi.org/10.3892/ol.2021.12487
  • Article Number: 226
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

One of the most commonly used drugs in chemotherapy, 5‑fluorouracil (5‑FU) has been shown to be effective in only 10‑15% of patients with colon cancer. Thus, studies of the mechanisms affecting 5‑FU sensitivity in these patients are necessary. The tumor suppressor protein p53 is a transcription factor that serves important roles in cell apoptosis by regulating the cell cycle. It has also been characterized as a key factor influencing drug sensitivity. Furthermore, accessible chromatin is a hallmark of active DNA regulatory elements and functions as a crucial epigenetic factor regulating cancer mechanisms. The present study assessed the genetic regulatory landscape in colon cancer by performing RNA sequencing and Assay for Transposase‑Accessible Chromatin sequencing, and investigated the effects of 5‑FU on chromatin accessibility and gene expression. Notably, while treatment with 5‑FU mediated global increases in chromatin accessibility, chromatin organization in several genomic regions differed depending on the expression status of p53. Since the occupancy of p53 does not overlap with accessible chromatin regions, the 5‑FU‑mediated changes in chromatin accessibility were not regulated by direct binding of p53. In the p53‑expressing condition, the 5‑FU‑mediated accessible chromatin region was primarily associated with genes encoding cell death pathways. Additionally, 5‑FU was revealed to induce open chromatin conformation at regions containing binding motifs for AP‑1 family transcription factors, which may drive expression of apoptosis pathway genes. In conclusion, expression of p53 may confer 5‑FU sensitivity by regulating chromatin accessibility of distinct genes associated with cell apoptosis in a transcription‑independent manner.
View Figures
View References

Related Articles

Journal Cover

March-2021
Volume 21 Issue 3

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Yang CM, Kang M, Jung W, Joo J, Kim Y, Choi Y and Kim H: p53 expression confers sensitivity to 5‑fluorouracil via distinct chromatin accessibility dynamics in human colorectal cancer. Oncol Lett 21: 226, 2021
APA
Yang, C.M., Kang, M., Jung, W., Joo, J., Kim, Y., Choi, Y., & Kim, H. (2021). p53 expression confers sensitivity to 5‑fluorouracil via distinct chromatin accessibility dynamics in human colorectal cancer. Oncology Letters, 21, 226. https://doi.org/10.3892/ol.2021.12487
MLA
Yang, C. M., Kang, M., Jung, W., Joo, J., Kim, Y., Choi, Y., Kim, H."p53 expression confers sensitivity to 5‑fluorouracil via distinct chromatin accessibility dynamics in human colorectal cancer". Oncology Letters 21.3 (2021): 226.
Chicago
Yang, C. M., Kang, M., Jung, W., Joo, J., Kim, Y., Choi, Y., Kim, H."p53 expression confers sensitivity to 5‑fluorouracil via distinct chromatin accessibility dynamics in human colorectal cancer". Oncology Letters 21, no. 3 (2021): 226. https://doi.org/10.3892/ol.2021.12487