ArticleCancer biology & therapy2023
KLF4 targets RAB26 and decreases 5-FU resistance through inhibiting autophagy in colon cancer.
Article in Cancer biology & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 21 citations in OpenAlex.
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Targeting the autophagic network: A new frontier in colorectal cancer chemotherapy response.CytoJournal · 2026Article
- Krüppel-Like Factor 4, a Hub Gate for Cell Crosstalk in Tumor Microenvironment.Cancer medicine · 2026Review
- Anti-Colon Cancer Effects of Lysate from Potential Probiotic Yeast Strains Derived from Human Breast Milk.Probiotics and antimicrobial proteins · 2025Article
- KLF4 in cancer chemoresistance: molecular mechanisms and therapeutic implications.Discover oncology · 2025Review
- Epithelial zinc finger protein in lung adenocarcinoma: prognostic biomarker with molecular and clinical implications.Hereditas · 2025Article
- CSF2 promotes chemoresistance in colorectal cancer by regulating Notch pathway.Discover oncology · 2025Article
- Effects of microplastics on chemo-resistance and tumorigenesis of colorectal cancer.Apoptosis : an international journal on programmed cell death · 2025Article
- KLF4: a multifunctional nexus connecting tumor progression and immune regulation.Frontiers in immunology · 2025Review
- Identifying core genes in keloid and investigating immune infiltration and pan-cancer associations using eQTL and machine learning.Bioinformatics advances · 2025Article
- Mitochondrial Deoxyguanosine Kinase Induces 5-Fluorouracil Chemotherapy Sensitivity through Autophagy.Current cancer drug targets · 2025Article
- The roles and mechanisms of APOL1 in the development of colorectal cancer.Journal of gastrointestinal oncology · 2024Article
- miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway.Molecular medicine reports · 2024Article
- Article
- The role of SIRT1 in autophagy and drug resistance: unveiling new targets and potential biomarkers in cancer therapy.Frontiers in pharmacology · 2024Review
- Nanoplatform-Mediated Autophagy Regulation and Combined Anti-Tumor Therapy for Resistant Tumors.International journal of nanomedicine · 2024Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAccumulating studies demonstrated that resistance of colon cancer (CC) to 5-fluorouracil (5-FU) contributes to adverse prognosis. We investigated how Kruppel-like factor 4 (KLF4) affected 5-FU resistance and autophagy in CC cells.
methodsKLF4 expression and its downstream target gene RAB26 in CC tissues was analyzed by bioinformatics analysis, and the effect of abnormal KLF4 expression on prognoses of CC patients was predicted. Luciferase reporter assay detected the targeted relationship between KLF4 and RAB26. The viability and apoptosis of CC cells were analyzed by CCK-8 and flow cytometry. The formation of intracellular autophagosomes was detected by confocal laser scanning microscopy and immunofluorescence staining. The mRNA and protein levels were assayed by qRT-PCR and western blot. A xenograft animal model was constructed to verify the function of KLF4. Rescue assay was employed to verify whether KLF4/RAB26 could affect 5-FU resistance in CC cells through autophagy.
resultsKLF4 and RAB26 were lowly expressed in CC. KLF4 correlated with patients' survival. KLF4 was down-regulated in 5-FU resistant CC cells. KLF4 overexpression suppressed the proliferation and 5-FU resistance of CC cells, and inhibited LC3 II/I expression and autophagosome formation. Autophagy activator Rapamycin or sh-RAB26 treatment reversed the impact of KLF4 overexpression on 5-FU resistance. In vivo assay verified that KLF4 inhibited 5-FU resistance in CC cells. Rescue experiments revealed that KLF4 targeted RAB26 to inhibit CC cell autophagy, resulting in decreasing the resistance to 5-FU.
conclusionKLF4 strengthened the sensitivity of CC cells to 5-FU by targeting RAB26 to restrain autophagy pathway.
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