Silencing of Spindle Apparatus Coiled-Coil Protein 1 Suppressed the Progression of Hepatocellular Carcinoma Through Farnesyltransferase-Beta and Increased Drug Sensitivity
Heliyon(2024)
摘要
Hepatocellular carcinoma (HCC) is the major cause of cancer-associated mortality worldwide. Despite great advances have been made on the treatment of HCC, the survival rate of patients remains poor. Spindle apparatus coiled-coil protein 1 (SPDL1) is involved in the development of various cancers in humans. However, the role of SPDL1 in HCC remains unclear. In this study, we found high expression of SPDL1 in HCC tissues as compared to normal samples. In vitro, silencing of SPDL1 induced HCC cell apoptosis, and suppressed HCC cell propagation and migration. In vivo, knockdown of SPDL1 inhibited the tumor growth of HCC cells. These findings indicated the tumor-promoting role of SPDL1 in HCC. Mechanistically, we identified farnesyltransferase-beta (FNTB) as the downstream target protein of SPDL1 based on immunoprecipitation and mass spectrometry, which were confirmed by western blotting. Rescue assay determined that FNTB played a tumor promoting role in SPDL1-trigger HCC cell growth. Overexpression of FNTB recovered HCC cell viability and migration in SPDL1 knockdown cells. We also found that silencing of SPDL1 increased the sensitivity of Huh7 cells to sorafenib and lenvatinib, suggesting that SPDL1 is a new therapeutic target in HCC. Collectivity, the present study identified a new axis SPDL1/FNTB involved in the progression of HCC. Hence, SPDL1/FNTB is a potential target for the treatment of HCC.
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关键词
SPDL1,FNTB,immunoprecipitation–mass spectrometry,high-content screening assay,migration,cell sensitivity
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