Open Access

Butyrate supplementation regulates expression of chromosome segregation 1‑like protein to reverse the genetic distortion caused by p53 mutations in colorectal cancer

  • Authors:
    • Chun-Chao Chang
    • Wei-Yu Kao
    • Chih-Yi Liu
    • Hui-Hsien Su
    • Yu-An Kan
    • Pao-Ying Lin
    • Wei-Chi Ku
    • Kang-Wei Chang
    • Ruey-Neng Yang
    • Chi-Jung Huang
  • View Affiliations

  • Published online on: April 13, 2022     https://doi.org/10.3892/ijo.2022.5354
  • Article Number: 64
  • Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The chromosome segregation 1‑like (CSE1L) protein, which regulates cellular mitosis and apoptosis, was previously found to be overexpressed in colorectal cancer (CRC) cells harboring mutations. Therefore, regulating CSE1L expression may confer chemotherapeutic effects against CRC. The gut microflora can regulate gene expression in colonic cells. In particular, metabolites produced by the gut microflora, including the short‑chain fatty acid butyrate, have been shown to reduce CRC risk. Butyrates may exert antioncogenic potential in CRC cells by modulating p53 expression. The present study evaluated the association between CSE1L expression and butyrate treatment from two non‑transformed colon cell lines (CCD‑18Co and FHC) and six CRC cell lines (LS 174T, HCT116 p53+/+, HCT116 p53‑/‑, Caco‑2, SW480 and SW620). Lentiviral knockdown of CSE1L and p53, reverse transcription‑quantitative PCR (CSE1L, c‑Myc and p53), western blotting [CSE1L, p53, cyclin (CCN) A2, CCNB2 and CCND1], wound healing assay (cell migration), flow cytometry (cell cycle analysis) and immunofluorescence staining (CSE1L and tubulin) were adopted to verify the effects of butyrate on CSE1L‑expressing CRC cells. The butyrate‑producing gut bacteria Butyricicoccus pullicaecorum was administered to mice with 1,2‑dimethylhydrazine‑induced colon tumors before the measurement of CSE1L expression. The effects of B. pullicaecorum on CSE1L expression were then assessed by immunohistochemical staining for CSE1L and p53 in tissues from CRC‑bearing mice. Non‑cancerous colon cells with the R273H p53 mutation or CRC cells haboring p53 mutations were found to exhibit significantly higher CSE1L expression levels. CSE1L knockdown in HCT116 p53‑/‑ cells resulted in G1‑and G2/M‑phase cell cycle arrest. Furthermore, in HCT116 p53‑/‑ cells, CSE1L expression was already high at interphase, increased at prophase, peaked during metaphase before declining at cytokinesis but remained relatively high compared with that in HCT116 expressing wild‑type p53. Significantly decreased expression levels of CSE1L were also observed in HCT116 p53‑/‑ cells that were treated with butyrate for 24 h. In addition, the migration of HCT116 p53‑/‑ cells was significantly decreased after CSE1L knockdown or butyrate treatment. Tumors with more intense nuclear p53 staining and weaker CSE1L staining were found in mice bearing DMH/DSS‑induced CRC that were administered with B. pullicaecorum. Taken together, the results indicated that butyrate can impair CSE1L‑induced tumorigenic potential. In conclusion, butyrate‑producing microbes, such as B. pullicaecorum, may reverse the genetic distortion caused by p53 mutations in CRC by regulating CSE1L expression levels.
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June-2022
Volume 60 Issue 6

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Spandidos Publications style
Chang C, Kao W, Liu C, Su H, Kan Y, Lin P, Ku W, Chang K, Yang R, Huang C, Huang C, et al: Butyrate supplementation regulates expression of chromosome segregation 1‑like protein to reverse the genetic distortion caused by p53 mutations in colorectal cancer. Int J Oncol 60: 64, 2022
APA
Chang, C., Kao, W., Liu, C., Su, H., Kan, Y., Lin, P. ... Huang, C. (2022). Butyrate supplementation regulates expression of chromosome segregation 1‑like protein to reverse the genetic distortion caused by p53 mutations in colorectal cancer. International Journal of Oncology, 60, 64. https://doi.org/10.3892/ijo.2022.5354
MLA
Chang, C., Kao, W., Liu, C., Su, H., Kan, Y., Lin, P., Ku, W., Chang, K., Yang, R., Huang, C."Butyrate supplementation regulates expression of chromosome segregation 1‑like protein to reverse the genetic distortion caused by p53 mutations in colorectal cancer". International Journal of Oncology 60.6 (2022): 64.
Chicago
Chang, C., Kao, W., Liu, C., Su, H., Kan, Y., Lin, P., Ku, W., Chang, K., Yang, R., Huang, C."Butyrate supplementation regulates expression of chromosome segregation 1‑like protein to reverse the genetic distortion caused by p53 mutations in colorectal cancer". International Journal of Oncology 60, no. 6 (2022): 64. https://doi.org/10.3892/ijo.2022.5354