CDP-Diacylglycerol Synthase 1 Promotes Proliferation, Invasion, and Metastasis in Hepatocellular Carcinoma

Xingyi Zhong, Chunting Zeng, Shulu Hu, Zhiqin Zhu, Junhao Lin, Fengsheng Chen

Article ID: 7776
Vol 38, Issue 1, 2024
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20243801.47
Received: 20 January 2024; Accepted: 20 January 2024; Available online: 20 January 2024; Issue release: 20 January 2024

Abstract

Background: CDP-diacylglycerol synthase 1 (CDS1), a functional protein regulating cell growth and lipid synthesis, is implicated in cancer development. Despite its potential role, the impact of CDS1 in hepatocellular carcinoma (HCC) remains elusive. This study aimed to explore the role of CDS1 on HCC progression. Finally, we elucidated whether CDS1 affects HCC pathogenesis and its associated signal transduction. Methods: CDS1 expression was assessed in tissue samples, correlating with clinical characteristics and prognostic outcomes in HCC. Vector, CDS1 overexpression, si-CDS1-2, and si-CDS1-3 groups were established using primary liver cancer tissues, adjacent normal tissues, human HCC cells, liver epithelial cells, and RNA/proteins extracts. In vitro and in vivo experiments were performed to determine the biological function and molecular basis of CDS1, including Cell Counting Kit-8, cell cycle, and 5-ethynyl-2′-deoxyuridine assays for proliferation, Transwell and Boyden assays for invasion and metastasis. Moreover, apoptosis assay, quantitative real-time polymerase chain reaction, and western blotting were shown. Results: Analysis of The Cancer Genome Atlas datasets revealed a significant increase in CDS1 expression in HCC, suggesting a potential influence on liver cancer cell growth, invasion, and apoptosis. Immunohistochemical analysis revealed elevated CDS1 protein levels in HCC samples compared to adjacent tissues. Furthermore, western blotting revealed a plausible carcinogenic role of CDS1 in HCC linked to the RAC-Alpha Serine/Threonine-Protein Kinase (AKT)-Mechanistic Target of Rapamycin (mTOR) signaling pathway. Finally, experimental findings confirmed that CDS1 promotes HCC proliferation, invasion, and metastasis while inhibiting apoptosis, potentially through the AKT-TSC2-mTOR pathway. Conclusions: CDS1 modulates the proliferation, migration, and invasion of liver cancer cells, impeding normal apoptotic processes. The underlying mechanism includes the activation of the AKT-TSC2-mTOR signaling pathway.


Keywords

CDP-diacylglycerol synthase 1;hepatocellular carcinoma;AKT signaling;oncology therapy


References

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