Related Experiment Video
Updated: Jun 20, 2025
Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells
Published on: June 30, 2023
MiR-200b-3p elevates 5-FU sensitivity in cholangiocarcinoma cells via autophagy inhibition by targeting KLF4
Feng Peng1, Ruizhi He1, Yuhui Liu1
1Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Abstract:
Cholangiocarcinoma is one of the most lethal human cancers, and chemotherapy failure is a major cause of recurrence and poor prognosis. We previously demonstrated that miR-200 family members are downregulated in clinical samples of cholangiocarcinoma and inhibit cholangiocarcinoma tumorigenesis and metastasis. However, the role of differentially expressed miR-200b-3p in 5-fluorouracil chemosensitivity remains unclear. Here, we examined how miR-200b-3p modulates 5-fluorouracil chemosensitivity in cholangiocarcinoma. We observed that miR-200b-3p was associated with 5-fluorouracil sensitivity in cholangiocarcinoma and increased 5-fluorouracil-induced mitochondrial apoptosis in cholangiocarcinoma cells. Mechanistically, miR-200b-3p suppressed autophagy in cholangiocarcinoma cells to mediate 5-fluorouracil sensitivity. Further, we identified KLF4 as an essential target of miR-200b-3p in cholangiocarcinoma. Notably, the miR-200b-3p/KLF4/autophagy pathway augmented the chemosensitivity of cholangiocarcinoma cells to 5-fluorouracil. Our findings underscore the key role of miR-200b-3p in chemosensitivity to 5-fluorouracil and highlight the miR-200b-3p/KLF4/autophagy axis as a potential therapeutic target for cholangiocarcinoma.
Insights
MicroRNA-200b-3p enhances cholangiocarcinoma sensitivity to 5-fluorouracil chemotherapy by suppressing autophagy. This miR-200b-3p/KLF4/autophagy pathway presents a novel therapeutic target for this lethal cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cholangiocarcinoma (CCA) is a lethal cancer with poor prognosis often linked to chemotherapy failure.
- The miR-200 family, including miR-200b-3p, is downregulated in CCA and inhibits tumor progression.
- The specific role of miR-200b-3p in 5-fluorouracil (5-FU) chemosensitivity in CCA is not well understood.
Purpose of the Study:
- To investigate the role of miR-200b-3p in modulating 5-FU chemosensitivity in cholangiocarcinoma.
- To elucidate the underlying molecular mechanisms by which miR-200b-3p affects 5-FU response.
- To identify potential therapeutic targets within the miR-200b-3p regulatory network for CCA treatment.
Main Methods:
- Analysis of miR-200b-3p expression and its correlation with 5-FU sensitivity in CCA.
- Assessment of miR-200b-3p's effect on 5-FU-induced apoptosis and autophagy in CCA cells.
- Identification of KLF4 as a direct target of miR-200b-3p and investigation of the miR-200b-3p/KLF4/autophagy pathway.
Main Results:
- miR-200b-3p expression levels were associated with 5-FU sensitivity in cholangiocarcinoma.
- miR-200b-3p significantly increased 5-FU-induced mitochondrial apoptosis in CCA cells.
- miR-200b-3p suppressed autophagy in CCA cells, mediating its effect on 5-FU sensitivity.
- KLF4 was identified as a key target gene regulated by miR-200b-3p.
- The miR-200b-3p/KLF4/autophagy pathway was shown to enhance CCA cell chemosensitivity to 5-FU.
Conclusions:
- miR-200b-3p plays a critical role in enhancing cholangiocarcinoma chemosensitivity to 5-fluorouracil.
- The miR-200b-3p/KLF4/autophagy axis represents a promising therapeutic strategy for overcoming 5-FU resistance in CCA.
- Targeting this pathway could improve treatment outcomes for patients with cholangiocarcinoma.
