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TRIM29 facilitates gemcitabine resistance via MEK/ERK pathway and is modulated by circRPS29/miR-770-5p axis in PDAC.
- Source :
-
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy [Drug Resist Updat] 2024 May; Vol. 74, pp. 101079. Date of Electronic Publication: 2024 Mar 12. - Publication Year :
- 2024
-
Abstract
- Aims: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Chemotherapy based on gemcitabine (GEM) remains the first-line drug for patients with advanced PDAC. However, GEM resistance impairs its therapeutic effectiveness. Therefore, identifying effective therapeutic targets are urgently needed to overcome GEM resistance.<br />Methods: The clinical significance of Tripartite Motif Containing 29 (TRIM29) was identified by exploring GEO datasets and TCGA database and its potential biological functions were predicted by GSEA analysis. The regulatory axis was established by bioinformatics analysis and validated by mechanical experiments. Then, in vitro and in vivo assays were performed to validate the roles of TRIM29 in PDAC GEM resistance.<br />Results: High TRIM29 expression was associated with poor prognosis of PDAC and functional experiments demonstrated that TRIM29 promoted GEM resistance in PDAC GEM-resistant (GR) cells. Furthermore, we revealed that circRPS29 promoted TRIM29 expression via competitive interaction with miR-770-5p and then activated MEK/ERK signaling pathway. Additionally, both in vitro and in vivo functional experiments demonstrated that circRPS29/miR-770-5p/TRIM29 axis promoted PDAC GEM resistance via activating MEK/ERK signaling pathway.<br />Conclusion: Our results identify the significance of the signaling axis, circRPS29/miR-770-5p/TRIM29-MEK/ERK, in PDAC GEM resistance, which will provide novel therapeutic targets for PDAC treatment.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Humans
Mice
Antimetabolites, Antineoplastic pharmacology
Antimetabolites, Antineoplastic therapeutic use
Cell Line, Tumor
Deoxycytidine analogs & derivatives
Deoxycytidine pharmacology
Deoxycytidine therapeutic use
DNA-Binding Proteins metabolism
DNA-Binding Proteins genetics
Gene Expression Regulation, Neoplastic drug effects
Mice, Nude
MicroRNAs genetics
MicroRNAs metabolism
Prognosis
RNA, Circular genetics
Xenograft Model Antitumor Assays
Carcinoma, Pancreatic Ductal drug therapy
Carcinoma, Pancreatic Ductal genetics
Carcinoma, Pancreatic Ductal pathology
Drug Resistance, Neoplasm genetics
Gemcitabine
MAP Kinase Signaling System drug effects
Pancreatic Neoplasms drug therapy
Pancreatic Neoplasms genetics
Pancreatic Neoplasms pathology
Transcription Factors genetics
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1532-2084
- Volume :
- 74
- Database :
- MEDLINE
- Journal :
- Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 38518727
- Full Text :
- https://doi.org/10.1016/j.drup.2024.101079