SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGF beta/PI3K/AKT/GSK3 beta pathway

文献类型： 外文期刊

第一作者： Xu, Pan

作者： Xu, Pan;Luo, Aoran;Ren, Hong;Luo, Qiang;Xiong, Chuan;Yan, Liang

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关键词： Hepatocellular carcinoma; SCUBE3; AKT; CCNE1; Cell proliferation

期刊名称：CANCER CELL INTERNATIONAL （ 影响因子：6.429； 五年影响因子：5.999 ）

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年卷期： 2022 年 22 卷 1 期

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收录情况： SCI

摘要： Objectives We aimed to verify the role of signal peptide-CUB-EGF-like domain-containing protein3 (SCUBE3) in the hepatocellular carcinoma (HCC) progression. Methods The role of SCUBE3 in HCC cell proliferation, apoptosis, and cell cycle in vitro were detected using MTT assay, colony formation assay, 5-ethynyl-2 '-deoxyuridine assay (EDU), Celigo cell counting assay, Caspase3/7 activity assay, and flow cytometry. The effect of SCUBE3 on HCC cell proliferation in vivo was inspected by a xenograft tumour model in nude mice. The related mechanisms were further studied. Results The level of SCUBE3 was upregulated in HCC tissues and cell lines. Knockdown of SCUBE3 inhibited proliferation, promoted apoptosis, and induced cell cycle arrest in HCC cell lines in vitro and in vivo. Screening of cell cycle-related proteins revealed that CCNL2, CDK6, CCNE1, and CCND1 exhibited a significantly different expression profile. We found that SCUBE3 may promote the proliferation of HCC cells by regulating CCNE1 expression. The pathway enrichment analysis showed that the TGF beta signalling pathway and the PI3K/AKT signalling pathway were significantly altered. Co-immunoprecipitation results showed that SCUBE3 binds to the TGF beta RII receptor. SCUBE3 knockdown inhibited the PI3K/AKT signalling pathway and the phosphorylation of GSK3 beta to inhibit its kinase activity. Conclusions SCUBE3 promotes HCC development by regulating CCNE1 via TGF beta/PI3K/AKT/GSK3 beta pathway. In addition, SCUBE3 may be a new molecular target for the clinical diagnosis and treatment of HCC.

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