Open Access

Knockdown of TRIM9 attenuates irinotecan‑induced intestinal mucositis in IEC‑6 cells by regulating DUSP6 expression via the P38 pathway

  • Authors:
    • Wenjun Zhao
    • Qingming Wang
  • View Affiliations

  • Published online on: October 20, 2021     https://doi.org/10.3892/mmr.2021.12507
  • Article Number: 867
  • Copyright: © Zhao 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

Intestinal mucositis is a common side effect of cancer chemotherapy and it limits the dose of chemotherapy given to a patient. Tripartite motif family (TRIM) proteins have been reported to be implicated in the regulation of cancer chemotherapy. The present study aimed to investigate the effect of TRIM9 on irinotecan‑induced intestinal mucositis in the rat intestinal epithelial cell line IEC‑6. The expression of several TRIMs, such as TRIM1, TRIM9, TRIM18, TRIM36, TRIM46 and TRIM67, was examined. After TRIM9 knockdown or overexpression by lentivirus infection, cell proliferation and apoptosis, epithelial barrier tight‑junction proteins, inflammatory cytokines, transepithelial electrical resistance (TEER) and FITC dextran were measured. Treatment with irinotecan significantly inhibited cell proliferation and induced cell apoptosis, TRIM9 expression, intestinal mucosal barrier impairment, the levels of inflammatory cytokines and P38 phosphorylation in IEC‑6 cells, while the expression levels of epithelial barrier tight‑junction protein ZO‑1 and Claudin‑4 were decreased. Knockdown of TRIM9 partly counteracted the effect of irinotecan treatment, and inhibition of P38 potently reversed the effect of TRIM9 overexpression in IEC‑6 cells. Moreover, co‑immunoprecipitation showed an interaction between TRIM9 and DUSP6 in IEC‑6 cells, and overexpression of DUSP6 notably counteracted the effect of TRIM9 overexpression. The results demonstrated that TRIM9 knockdown may benefit patients with intestinal mucositis by inhibiting inflammatory cytokine expression and repairing intestinal barrier functions, which was probably due to inhibition of the activation of the P38 pathway via targeting DUSP6.
View Figures
View References

Related Articles

Journal Cover

December-2021
Volume 24 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhao W and Zhao W: Knockdown of TRIM9 attenuates irinotecan‑induced intestinal mucositis in IEC‑6 cells by regulating DUSP6 expression via the P38 pathway. Mol Med Rep 24: 867, 2021
APA
Zhao, W., & Zhao, W. (2021). Knockdown of TRIM9 attenuates irinotecan‑induced intestinal mucositis in IEC‑6 cells by regulating DUSP6 expression via the P38 pathway. Molecular Medicine Reports, 24, 867. https://doi.org/10.3892/mmr.2021.12507
MLA
Zhao, W., Wang, Q."Knockdown of TRIM9 attenuates irinotecan‑induced intestinal mucositis in IEC‑6 cells by regulating DUSP6 expression via the P38 pathway". Molecular Medicine Reports 24.6 (2021): 867.
Chicago
Zhao, W., Wang, Q."Knockdown of TRIM9 attenuates irinotecan‑induced intestinal mucositis in IEC‑6 cells by regulating DUSP6 expression via the P38 pathway". Molecular Medicine Reports 24, no. 6 (2021): 867. https://doi.org/10.3892/mmr.2021.12507