ArticleInternational journal of molecular sciences2019
Role of SIRT-3, p-mTOR and HIF-1α in Hepatocellular Carcinoma Patients Affected by Metabolic Dysfunctions and in Chronic Treatment with Metformin.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Deciphering the role of sirtuins in cancer immunoregulation through molecular cross-talk and docking-based interaction.Molecular biology reports · 2026Review
- Role of SIRT3 in digestive system diseases and therapeutic prospects (Review).International journal of molecular medicine · 2026Review
- Research Progress on the Molecular Mechanism of Metformin Regulating AMPK Signaling Pathway in Inhibiting Liver Cancer.OncoTargets and therapy · 2026Review
- SIRT3, a New Hope in Liver Diseases from Pathogenic Mechanisms to Therapeutic Strategies.Current pharmaceutical biotechnology · 2025Review
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- The dual role of sirtuins in cancer: biological functions and implications.Frontiers in oncology · 2024Review
- NADH elevation during chronic hypoxia leads to VHL-mediated HIF-1α degradation via SIRT1 inhibition.Cell & bioscience · 2023Article
- Review
- Sirtuin1 attenuates acute liver failure by reducing reactive oxygen speciesWorld journal of gastroenterology · 2022Article
- Bioinformatic Analysis of the Effect of theBioMed research international · 2022Article
- Expression of caspase-3 and hypoxia inducible factor 1α in hepatocellular carcinoma complicated by hemorrhage and necrosis.World journal of clinical cases · 2021Article
- Sorafenib in the Treatment of Virus-Related HCC: Differences Between HCV and HBV.OncoTargets and therapy · 2021Article
- Mitophagy Disequilibrium, a Prominent Pathological Mechanism in Metabolic Heart Diseases.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- Hepatocellular carcinoma in non-alcoholic fatty liver disease-a review of an emerging challenge facing clinicians.Hepatobiliary surgery and nutrition · 2021Review
- Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma: Preliminary Toxicity and Activity Data in Dogs.Cancers · 2020Article
- A novel germline gain-of-function HIF2A mutation in hepatocellular carcinoma with polycythemia.Aging · 2020Article
- Immune Checkpoint Inhibitors in the Treatment of HCC.Frontiers in oncology · 2020Review
- Article
- The role of PNI to predict survival in advanced hepatocellular carcinoma treated with Sorafenib.PloS one · 2020Article
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Authors and funding
19 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The incidence of hepatocellular carcinoma deriving from metabolic dysfunctions has increased in the last years. Sirtuin- (SIRT-3), phospho-mammalian target of rapamycin (p-mTOR) and hypoxia-inducible factor- (HIF-1α) are involved in metabolism and cancer. However, their role in hepatocellular carcinoma (HCC) metabolism, drug resistance and progression remains unclear. This study aimed to better clarify the biological and clinical function of these markers in HCC patients, in relation to the presence of metabolic alterations, metformin therapy and clinical outcome. A total of 70 HCC patients were enrolled: 48 and 22 of whom were in early stage and advanced stage, respectively. The expression levels of the three markers were assessed by immunohistochemistry and summarized using descriptive statistics. SIRT-3 expression was higher in diabetic than non-diabetic patients, and in metformin-treated than insulin-treated patients. Interestingly, p-mTOR was higher in patients with metabolic syndrome than those with different etiology, and, similar to SIRT-3, in metformin-treated than insulin-treated patients. Moreover, our results describe a slight, albeit not significant, benefit of high SIRT-3 and a significant benefit of high nuclear HIF-1α expression in early-stage patients, whereas high levels of p-mTOR correlated with worse prognosis in advanced-stage patients. Our study highlighted the involvement of SIRT-3 and p-mTOR in metabolic dysfunctions that occur in HCC patients, and suggested SIRT-3 and HIF-1α as predictors of prognosis in early-stage HCC patients, and p-mTOR as target for the treatment of advanced-stage HCC.
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