ArticleOncoTargets and therapy2018
Metformin induces miR-378 to downregulate the CDK1, leading to suppression of cell proliferation in hepatocellular carcinoma.
Article in OncoTargets and therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- Hispidulin Suppresses Hepatocellular Carcinoma Proliferation by Targeting PI3K-Akt Pathway: A Network Pharmacology and Experimental Validation Study.Journal of hepatocellular carcinoma · 2026Article
- Transferrin promotes fatty acid oxidation and liver tumor growth through PHD2-mediated PPARα hydroxylation in an iron-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Metformin inhibits the proliferation of hepatocellular carcinoma cells through inducing ferroptosis analyzed by phosphoproteomics.Frontiers in oncology · 2025Article
- Article
- Prognostic modeling of hepatocellular carcinoma based on T-cell proliferation regulators: a bioinformatics approach.Frontiers in immunology · 2024Article
- Arecoline promotes proliferation and migration of human HepG2 cells through activation of the PI3K/AKT/mTOR pathway.Hereditas · 2022Article
- Role of metformin in the diagnosis, prevention, and treatment of hepatocellular carcinoma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- Identification of key genes and carcinogenic pathways in hepatitis B virus-associated hepatocellular carcinoma through bioinformatics analysis.Annals of hepato-biliary-pancreatic surgery · 2022Article
- Influence of Hyperglycemia on the Prognosis of Patients with Diffuse Large B-Cell Lymphoma.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- Study on the mechanism of action ofFrontiers in pharmacology · 2022Article
- DEPDC1B promotes development of cholangiocarcinoma through enhancing the stability of CDK1 and regulating malignant phenotypes.Frontiers in oncology · 2022Article
- Inhibitors of Mitochondrial Dynamics Mediated by Dynamin-Related Protein 1 in Pulmonary Arterial Hypertension.Frontiers in cell and developmental biology · 2022Review
- Endometriosis Cell Proliferation Induced by Bone Marrow Mesenchymal Stem Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- miR-378a-3p Participates in Metformin's Mechanism of Action on C2C12 Cells under Hyperglycemia.International journal of molecular sciences · 2021Article
- CDK1, CCNB1, and CCNB2 are Prognostic Biomarkers and Correlated with Immune Infiltration in Hepatocellular Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Bioinformatics analysis to reveal key biomarkers for early and late hepatocellular carcinoma.Translational cancer research · 2020Article
- miR‑378 in combination with ultrasonic irradiation and SonoVue microbubbles transfection inhibits hepatoma cell growth.Molecular medicine reports · 2020Article
- miR-378a: a new emerging microRNA in metabolism.Cellular and molecular life sciences : CMLS · 2020Review
- MicroRNA-124 and microRNA-378 inhibit the proliferation and invasion of colorectal cancer by upregulating KiSS1.Translational cancer research · 2020Article
- Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells.Journal of Cancer · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
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Abstract
Metformin is one of the extensively and most commonly used oral antihyperglycemic agents, but it has been shown to exert antineoplastic effects in many cancer cells. Recent studies have confirmed that metformin has an antitumor effect on hepatocellular carcinoma (HCC). However, the molecular mechanism underlying this effect needs to be further studied. MATERIALS AND
methodsCDK1 and miR-378 expression was analyzed by western blotting and real-time PCR assays. We confirmed the association between miR-378 and CDK1 by dual luciferase reporter assay. The role of the miR-378/CDK1 pathway in proliferation, cell cycle and apoptosis was examined in vitro. The effect of miR-378 on HCC tumor growth was evaluated in nude xenograft mouse model.
resultsOur study found that metformin significantly inhibited the HCC cell proliferation via inducing G2/M arrest. At the same time, metformin efficiently decreased CDK1 expression and elevated miR-378 level. Moreover, the upregulation of miR-378 also repressed HCC cell proliferation by causing G2/M arrest and inhibited tumor growth. Additionally, we demonstrated that miR-378 directly targeted CDK1 3'UTR and downregulated CDK1 mRNA and protein levels. Furthermore, metformin treatment could not decrease CDK1 expression, suppress HCC cell proliferation, and induce G2/M cell cycle arrest. DISCUSSION: Metformin-suppressed HCC cell proliferation was dependent on the inhibitory effect of miR-378 on CDK1 expression. Taken together, we concluded that metformin inhibited HCC cell proliferation via modulating miR-378/CDK1 axis.
conclusionCollectively, the current results provide the first evidence, to our knowledge, that miR-378/CDK1 axis is involved in metformin modulating the proliferation of HCC cells, which suggests a novel molecular mechanism underlying the thera peutic effect of metformin on HCC.
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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.