Oncogenic TRIM31 confers gemcitabine resistance in pancreatic cancer via activating the NF-κB signaling pathway.

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  • Author(s): Yu C;Yu C; Chen S; Chen S; Guo Y; Guo Y; Sun C; Sun C
  • Source:
    Theranostics [Theranostics] 2018 May 11; Vol. 8 (12), pp. 3224-3236. Date of Electronic Publication: 2018 May 11 (Print Publication: 2018).
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Ivyspring International Publisher Country of Publication: Australia NLM ID: 101552395 Publication Model: eCollection Cited Medium: Internet ISSN: 1838-7640 (Electronic) Linking ISSN: 18387640 NLM ISO Abbreviation: Theranostics Subsets: MEDLINE
    • Publication Information:
      Original Publication: Wyoming, N.S.W. : Ivyspring International Publisher, 2011-
    • Subject Terms:
      Drug Resistance, Neoplasm* ; Signal Transduction*; Antimetabolites, Antineoplastic/*pharmacology ; Deoxycytidine/*analogs & derivatives ; NF-kappa B/*metabolism ; Pancreatic Neoplasms/*drug therapy ; Tripartite Motif Proteins/*metabolism ; Ubiquitin-Protein Ligases/*metabolism; Aged ; Animals ; Blotting, Western ; Deoxycytidine/pharmacology ; Disease Models, Animal ; Female ; Gene Expression Profiling ; Heterografts ; Humans ; Male ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Transplantation ; Pancreatic Neoplasms/pathology ; Real-Time Polymerase Chain Reaction ; Tumor Cells, Cultured ; Gemcitabine
    • Abstract:
      Background: Drug resistance is well known as a major obstacle for cancer recurrence and treatment failure, leading to poor survival in pancreatic cancer, which is a highly aggressive tumor. Identifying effective strategies to overcome drug resistance would have a significant clinical impact for patients with pancreatic cancer. Methods: The protein and mRNA expression of TRIM31 in pancreatic cancer cell lines and patient tissues were determined using Real-time PCR and Western blot, respectively. 89 human pancreatic cancer tissue samples were analyzed by IHC to investigate the association between TRIM31 expression and the clinicopathological characteristics of pancreatic cancer patients. Functional assays, such as MTT, FACS, and Tunel assay used to determine the oncogenic role of TRIM31 in human pancreatic cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM31 promotes chemoresistance in pancreatic cancer cells. Results: The expression of TRIM31was markedly upregulated in pancreatic cancer cell lines and tissues, and high TRIM31 expression was associated with an aggressive phenotype and poor prognosis with pancreatic cancer patients. TRIM31 overexpression confers gemcitabine resistance on pancreatic cancer cells; however, inhibition of TRIM31 sensitized pancreatic cancer cell lines to gemcitabine cytotoxicity both in vitro and in vivo . Additionally, TRIM31 upregulated the levels of nuclear p65 by promoting K63-linked polyubiquitination of tumor necrosis factor receptor-associated factor 2 (TRAF2) and sustained the activation of nuclear transcription factor kappa B (NF-κB) in pancreatic cancer cells. Conclusions: Our findings provided evidence that TRIM31 is a potential therapeutic target for patients with pancreatic cancer. Targeting TRIM31 signaling may be a promising strategy to enhance gemcitabine response during pancreatic cancer chemo-resistance.
      Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
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    • Contributed Indexing:
      Keywords: NF-κB signaling; TRIM31; chemoresistance; pancreatic cancer
    • Accession Number:
      0 (Antimetabolites, Antineoplastic)
      0 (NF-kappa B)
      0 (Tripartite Motif Proteins)
      0W860991D6 (Deoxycytidine)
      EC 2.3.2.27 (TRIM31 protein, human)
      EC 2.3.2.27 (Ubiquitin-Protein Ligases)
      0 (Gemcitabine)
    • Publication Date:
      Date Created: 20180623 Date Completed: 20190827 Latest Revision: 20221207
    • Publication Date:
      20221213
    • Accession Number:
      PMC6010981
    • Accession Number:
      10.7150/thno.23259
    • Accession Number:
      29930725