ArticleCell death and differentiation2023
CRISPR/Cas9-mediated inactivation of miR-34a and miR-34b/c in HCT116 colorectal cancer cells: comprehensive characterization after exposure to 5-FU reveals EMT and autophagy as key processes regulated by miR-34.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Role of epithelial-mesenchymal transition (EMT) in malignancies: current status and future prospects.Signal transduction and targeted therapy · 2026Review
- The Mechanistic Crosstalk between Probiotics, ncRNAs, and Autophagy: Implications for Colorectal Cancer Precision Medicine.Expert reviews in molecular medicine · 2026Review
- Investigating autophagy and miRNAs as therapeutic targets in leukemia.Discover oncology · 2026Review
- MiR-5100 promotes the malignant phenotype of triple-negative breast cancer cells by targeting SMAD4 and predicts poor prognosis.World journal of surgical oncology · 2026Article
- Vitamin D receptor loss promotes endometrial fibrosis via autophagy-mediated epithelial-mesenchymal transition.Genes & diseases · 2026Article
- Environmental Fluoride Compromises Male Fertility: Differentially Modulated miR-34a-5p Targets REST to Regulate Autophagy in Testicular Somatic Cells.Research (Washington, D.C.) · 2026Article
- Exploring the therapeutic potential of microRNAs: targeted gene regulation strategies for enhanced cancer therapy.Journal, genetic engineering & biotechnology · 2025Review
- Multi-omic characterization of consensus molecular subtype 1 (CMS1) colorectal cancer with dampened immune response improves precision medicine.Molecular oncology · 2025Article
- Epithelial-mesenchymal transition in colorectal cancer metastasis and progression: molecular mechanisms and therapeutic strategies.Cell death discovery · 2025Review
- Progress on multifunctional transmembrane protein ATG9A.Cell communication and signaling : CCS · 2025Review
- YBX1 promotes 5-Fluorouracil resistance in gastric cancer via m5C-dependent ATG9A mRNA stabilization through autophagy.Oncogene · 2025Article
- AHNAK2 confers 5-fluorouracil resistance in colorectal cancer via activation of the AKT/GSK-3β signaling axis.Clinical and experimental medicine · 2025Article
- Epigenetic Silencing of miR-218-5p Modulates BIRC5 and DDX21 Expression to Promote Colorectal Cancer Progression.International journal of molecular sciences · 2025Article
- Identification of Autophagy-Related Genes in Patients with Acute Spinal Cord Injury and Analysis of Potential Therapeutic Targets.Molecular neurobiology · 2025Article
- Crosstalk between non-coding RNAs and programmed cell death in colorectal cancer: implications for targeted therapy.Epigenetics & chromatin · 2025Review
- Non-coding RNAs: emerging biomarkers and therapeutic targets in cancer and inflammatory diseases.Frontiers in oncology · 2025Review
- Dual Regulation and Clinical Application of miR-34 in Virus-Related Tumors Through Anti-Viral Immunity and Tumor Suppression.Drug design, development and therapy · 2025Review
- Aluminum Concentration Is Associated with Tumor Mutational Burden and the Expression of Immune Response Biomarkers in Colorectal Cancers.International journal of molecular sciences · 2024Article
- Targeting the autophagy-miRNA axis in prostate cancer: toward novel diagnostic and therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Let's make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment.Cell biology and toxicology · 2024Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The miR-34a and miR-34b/c encoding genes represent direct targets of the p53 transcription factor, and presumably mediate part of the tumor suppressive effects of p53. Here, we sought to determine their functional relevance by inactivating miR-34a and/or miR-34b/c using a CRISPR/Cas9 approach in the colorectal cancer (CRC) cell line HCT116. Concomitant deletion of miR-34a and miR-34b/c resulted in significantly reduced suppression of proliferation after p53 activation, enhanced migration, invasion and EMT, as well as reduced sensitivity to chemotherapeutics, increased stress-induced autophagic flux, decreased apoptosis and upregulation of autophagy-related genes after 5-FU treatment. However, inactivation of singular miR-34a or miR-34b/c had little effects on the aforementioned processes. RNA-Seq analysis revealed that concomitant deletion of miR-34a/b/c caused EMT signature enrichment, impaired gene repression by the p53-DREAM pathway and elevated autophagy after 5-FU treatment. A gene signature comprised of mRNAs significantly upregulated after combined inactivation of miR-34a and miR-34b/c showed a significant association with the invasive colon cancer subtype CMS4 and poor overall survival in two CRC patient cohorts, and with 5-FU resistance in CRC cell lines. In miR-34a/b/c-deficient cells the upregulated miR-34 target FOXM1 directly induced p62 and ATG9A, which increased autophagy and consequently attenuated apoptosis and rendered the miR-34a/b/c-KO cells more resistant to 5-FU. Inhibition of autophagy by depletion of ATG9A or chloroquine re-sensitized miR-34a/b/c-deficient HCT116 cells to 5-FU. In summary, our findings show a complementary role of miR-34a and miR-34b/c in the regulation of EMT and autophagy which may be relevant for CRC therapy in the future.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.