ArticleCellular and molecular gastroenterology and hepatology2022
Loss of SPTBN1 Suppresses Autophagy Via SETD7-mediated YAP Methylation in Hepatocellular Carcinoma Initiation and Development.
Article in Cellular and molecular gastroenterology and hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting YAP: mechanistic breakthroughs and therapeutic prospects in reversing organ fibrosis.Molecular and cellular biochemistry · 2026Review
- Mechanobiology of the Hippo-YAP Signaling Network.Cold Spring Harbor perspectives in biology · 2026Article
- SPTBN1 overexpression ameliorates atherosclerosis by inhibiting oxidative stress and inflammation via regulating the TRIM37/TRAF2/NF-κB pathway.European journal of medical research · 2025Article
- YAP/TAZ: An epitome of tumorigenesis.Cancer letters · 2025Review
- Posttranslational modifications of YAP/TAZ: molecular mechanisms and therapeutic opportunities.Cellular & molecular biology letters · 2025Review
- Unveiling the potency of ZnO and CuO nanocomposites in combating hepatocellular carcinoma by inducing cell death and suppressing migration.Scientific reports · 2025Article
- Recent advances in targeting obesity, with a focus on TGF-β signaling and vagus nerve innervation.Bioelectronic medicine · 2025Review
- Lysine methyltransferase SETD7 in cancer: functions, molecular mechanisms and therapeutic implications.Molecular biology reports · 2025Review
- A Novel tRF, HCETSR, Derived From tRNA-Glu/TTC, Inhibits HCC Malignancy by Regulating the SPBTN1-catenin Complex Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting the Hippo/YAP1 signaling pathway in hepatocellular carcinoma: From mechanisms to therapeutic drugs (Review).International journal of oncology · 2024Review
- Lysine-specific methyltransferase Set7/9 in stemness, differentiation, and development.Biology direct · 2024Review
- Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression.Journal of cellular and molecular medicine · 2024Article
- Article
- YAP/TAZ: Molecular pathway and disease therapy.MedComm · 2023Review
- Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.Cellular & molecular biology letters · 2023Review
- SPTBN1 attenuates rheumatoid arthritis synovial cell proliferation, invasion, migration and inflammatory response by binding to PIK3R2.Immunity, inflammation and disease · 2022Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsLoss of Spectrin beta, non-erythrocytic 1 (SPTBN1) plays an important role in the carcinogenesis of hepatocellular carcinoma (HCC); however, the mechanisms underlying its involvement remain poorly understood. Defects in autophagy contribute to hepatic tumor formation. Hence, in this study, we explored the role and mechanism of SPTBN1 in the autophagy of hepatic stem cells (HSCs) and HCC cells.
methodsExpansion, autophagy, and malignant transformation of HSCs were detected in the injured liver of Sptbn1
resultsWe found that heterozygous SPTBN1 knockout accelerated liver tumor development with 3,5-diethoxycarbonyl-1,4-dihydrocollidine induction. Rapamycin promoted autophagy in murine HSCs and reversed the increased malignant transformation induced by heterozygous SPTBN1 deletion. Loss of SPTBN1 also decreased autophagy and increased YAP stability and nuclear localization in human HCC cells and tissues, whereas YAP inhibition attenuated the effects of SPTBN1 deficiency on autophagy. Finally, we found that SPTBN1 positively regulated the expression of suppressor of variegation 3-9-enhancer of zeste-trithorax domain containing lysine methyltransferase 7 to promote YAP methylation, which may lead to YAP degradation and inactivation.
conclusionsOur findings provide the first demonstration that loss of SPTBN1 impairs autophagy of HSCs to promote expansion and malignant transformation during hepatocarcinogenesis. SPTBN1 also cooperates with suppressor of variegation 3-9-enhancer of zeste-trithorax domain containing lysine methyltransferase 7 to inactive YAP, resulting in enhanced autophagy of HCC cells. These results may open new avenues targeting SPTBN1 for the prevention and treatment of HCC.
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