ArticleCell death & disease2022
MiRNA-124-3p.1 sensitizes hepatocellular carcinoma cells to sorafenib by regulating FOXO3a by targeting AKT2 and SIRT1.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Tissue-Specific Isolation of Hepatocyte Extracellular Vesicles From Human Plasma Enables Tissue-Resolved Proteomic and miRNA Profiling.Journal of extracellular vesicles · 2026Article
- Hepatic p38γ exacerbates acetaminophen‑induced acute liver injury via PI3K/Akt‑dependent mechanisms.International journal of molecular medicine · 2026Article
- MicroRNA-SIRT1 crosstalk in liver diseases: molecular regulation of metabolism, inflammation, and cell survival.Molecular biology reports · 2026Review
- Multidimensional Regulatory Network and Spatiotemporal Specificity of FOXO Transcription Factors in Digestive System Tumors: Recent Advances.International journal of molecular sciences · 2026Review
- Multifaceted roles of miR‑124 in cancer: Molecular mechanisms and clinical prospects (Review).International journal of oncology · 2026Review
- The possible role of sirtuins and MiRNAs in gastrointestinal cancers: special focus on Sirt1.Cancer cell international · 2026Review
- Review
- Resistance of first-line targeted drugs in hepatocellular carcinoma: the epigenetic regulation mechanisms.Cell death & disease · 2025Review
- SIRT1-Mediated Redox and Senescence Regulation in Cancer: Mechanisms and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2025Review
- Upregulation of circRNA_0002286 protects against brain ischemia/reperfusion injury after remote ischemic postconditioning via microRNA-124-3p/VLCAD axis.Journal of molecular histology · 2025Article
- Downregulation of forkhead box O1 (FOXO1) acetylation ameliorates cognitive dysfunction by inhibiting endoplasmic reticulum stress-regulated neuronal apoptosis in APP/PS1 transgenic mice.Neuroprotection (Chichester, England) · 2025Article
- Exploring the Molecular Mechanism of 1,25(OH)Current issues in molecular biology · 2025Article
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Exosomal miR-6126 as a novel therapeutic target for overcoming resistance of anti-cancer effect in hepatocellular carcinoma.BMC cancer · 2024Article
- MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Review
- Liver Biopsy Handling of Metabolic-Associated Fatty Liver Disease (MAFLD): the Children's Hospital of Eastern Ontario grossing protocol.Therapeutic advances in endocrinology and metabolism · 2024Review
- Elevated expression patterns of P-element Induced Wimpy Testis (PIWI) transcripts are potential candidate markers for Hepatocellular Carcinoma.Cancer biomarkers : section A of Disease markers · 2024Article
- MicroRNAs in Hepatocellular Carcinoma: Insights into Regulatory Mechanisms, Clinical Significance, and Therapeutic Potential.Cancer management and research · 2024Review
- Role of Non-Coding RNAs in Hepatocellular Carcinoma Progression: From Classic to Novel Clinicopathogenetic Implications.Cancers · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a multikinase inhibitor, sorafenib is commonly used to treat patients with advanced hepatocellular carcinoma (HCC), however, acquired resistance to sorafenib is a major obstacle to the effectiveness of this treatment. Thus, in this study, we investigated the mechanisms underlying sorafenib resistance as well as approaches devised to increase the sensitivity of HCC to sorafenib. We demonstrated that miR-124-3p.1 downregulation is associated with early recurrence in HCC patients who underwent curative surgery and sorafenib resistance in HCC cell lines. Regarding the mechanism of this phenomenon, we identified FOXO3a, an important cellular stress transcriptional factor, as the key factor in the function of miR-124-3p.1 in HCC. We showed that miR-124-3p.1 binds directly to AKT2 and SIRT1 to reduce the levels of these proteins. Furthermore, we showed that AKT2 and SIRT1 phosphorylate and deacetylate FOXO3a. We also found that miR-124-3p.1 maintains the dephosphorylation and acetylation of FOXO3a, leading to the nuclear location of FOXO3a and enhanced sorafenib-induced apoptosis. Moreover, the combination of miR-124-3p.1 mimics and sorafenib significantly enhanced the curative efficacy of sorafenib in a nude mouse HCC xenograft model. Collectively, our data reveal that miR-124-3p.1 represents a predictive indicator of early recurrence and sorafenib sensitivity in HCC. Furthermore, we demonstrate that miR-124-3p.1 enhances the curative efficacy of sorafenib through dual effects on FOXO3a. Thus, the miR-124-3p.1-FOXO3a axis is implicated as a potential target for the diagnosis and treatment of HCC.
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Registered trials
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.