ArticleBiochimica et biophysica acta. Molecular basis of disease2019
Sesn3 deficiency promotes carcinogen-induced hepatocellular carcinoma via regulation of the hedgehog pathway.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2019. 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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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- SESN3 restrains the progress of idiopathic pulmonary fibrosis by targeting the activity of FOSL2.Biology direct · 2025Article
- Review
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- Transcriptomics and metabolomics insights into the seasonal dynamics of meat quality in yak on the Qinghai-Tibetan Plateau.BMC genomics · 2024Article
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- Role of sestrins in metabolic and aging-related diseases.Biogerontology · 2024Review
- Identifying the Carcinogenic Mechanism of Malignant Struma Ovarii Using Whole-Exome Sequencing and DNA Methylation Analysis.Current issues in molecular biology · 2023Article
- Whole-exome sequencing identified recurrent and novel variants in benzene-induced leukemia.BMC medical genomics · 2023Article
- Identification and Interaction Analysis of Molecular Markers in Pancreatic Ductal Adenocarcinoma by Bioinformatics and Next-Generation Sequencing Data Analysis.Bioinformatics and biology insights · 2023Article
- A strategy for the treatment of gastrointestinal cancer: Targeting tumor senescent cells.Frontiers in molecular biosciences · 2023Review
- Circ_0036412 affects the proliferation and cell cycle of hepatocellular carcinoma via hedgehog signaling pathway.Journal of translational medicine · 2022Article
- Oncogenic role of early growth response-1 in liver cancer through the regulation of the microRNA-675/sestrin 3 and the Wnt/β-catenin signaling pathway.Bioengineered · 2021Article
- Knockdown of microRNA-214-3p Promotes Tumor Growth and Epithelial-Mesenchymal Transition in Prostate Cancer.Cancers · 2021Article
- Sestrins in Physiological Stress Responses.Annual review of physiology · 2021Review
- Review
- Sestrins: Darkhorse in the regulation of mitochondrial health and metabolism.Molecular biology reports · 2020Review
- SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Sestrin 3 (Sesn3) belongs to a small protein family that has been implicated in multiple biological processes including anti-oxidative stress, anti-aging, cell signaling, and metabolic homeostasis. However, the role of Sesn3 in hepatocellular carcinoma (HCC) remains unclear. Here we generated a Sesn3 knockout mouse model and induced HCC development by a combination of a single dose of diethylnitrosamine and chronic feeding of a choline deficient-high fat diet. After 6 months of the dietary treatment, Sesn3 knockout mice developed more severe HCC with higher levels of alpha-fetoprotein, arginase 1, and cytokeratin 19, but also higher metastatic rates than wild-type mice. Histological analysis revealed elevated extracellular matrix and cancer stem cell markers including Acta2, Cd44, and Cd133. Signaling analysis showed activated IL6-Stat3 and Akt pathways. Biochemical and microscopic analyses uncovered a novel inhibitory regulation of Gli2, a downstream transcription factor of the hedgehog signaling, by Sesn3. Two of the Gli2-regulated genes - Pdgfrb and Cd44 were upregulated in the Sesn3-deficient liver tissue. In conclusion, our data suggest that Sesn3 plays a critical tumor suppressor role in the liver partly through the inhibition of the hedgehog signaling.
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