液泡分选相关蛋白 72 同源物（VPS72）与赖氨酸乙酰转移酶 5（KAT5）结合，通过调节磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）信号通路促进肝癌的增殖、侵袭和迁移。
Vacuolar protein sorting-associated protein 72 homolog (VPS72) binding to lysine acetyltransferase 5 (KAT5) promotes the proliferation, invasion and migration of hepatocellular carcinoma through regulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.
机构信息
Department of Hepatobiliary Surgery, The Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China.
出版信息
Bioengineered. 2022 Apr;13(4):9197-9210. doi: 10.1080/21655979.2022.2056692.
Hepatocellular carcinoma, a fatal malignancy that occurs in the liver, poses a major public health challenge. This paper attempted to clarify the role and mechanism of vacuolar protein sorting-associated protein 72 homolog (VPS72) in the progression of hepatocellular carcinoma. Firstly, VPS72 expression in hepatocellular carcinoma tissues and the prognostic correlation were analyzed by GEPIA2 database. Western blotting and RT-qPCR assays were used to evaluate VPS72 expression in several hepatocellular carcinoma cell lines. Then, cell proliferation was assessed by cell counting kit-8 and colony formation in HuH-7 cells with VPS72 silencing. Measurement of cell invasion and migration by transwell and wound healing assays. Next, the relationship between VPS72 and lysine acetyltransferase 5 (KAT5) was predicted by bioGRID, STRING and GEIPA2 databases, which was confirmed by Co-immunoprecipitation assay. Subsequently, KAT5 was overexpressed to explore whether VPS72 could regulate the progression of hepatocellular carcinoma by binding to KAT5. And the expression of proteins related to PI3K/AKT signaling was tested with western blotting. Results indicated that VPS72 was highly expressed in hepatocellular carcinoma tissues and cell lines and was associated with poor prognosis. VPS72 knockdown inhibited the proliferation, invasion and migration of HuH-7 cells. In addition, VPS72 could bind to KAT5. KAT5 overexpression reversed the suppressive impacts of VPS72 knockdown on the proliferation, invasion and migration in HuH-7 cells. Besides, VPS72 silencing downregulated p-PI3K and p-AKT expression, which was restored by KAT5 overexpression. Collectively, VPS72 binding to KAT5 promotes the progression of hepatocellular carcinoma through the regulation of PI3K/AKT signaling pathway.
肝细胞癌是一种发生在肝脏的致命恶性肿瘤，是一个重大的公共卫生挑战。本文试图阐明液泡蛋白分选相关蛋白 72 同源物（VPS72）在肝细胞癌进展中的作用和机制。首先，通过 GEPIA2 数据库分析 VPS72 在肝细胞癌组织中的表达及其与预后的相关性。通过 Western blot 和 RT-qPCR 检测几种肝细胞癌细胞系中 VPS72 的表达。然后，通过细胞计数试剂盒-8 和 VPS72 沉默的 HuH-7 细胞中的集落形成评估细胞增殖。通过 Transwell 和划痕愈合实验测量细胞侵袭和迁移。接下来，通过生物 GRID、STRING 和 GEIPA2 数据库预测 VPS72 与赖氨酸乙酰转移酶 5（KAT5）之间的关系，通过 Co-immunoprecipitation 实验进行验证。随后，过表达 KAT5 以探讨 VPS72 是否可以通过与 KAT5 结合来调节肝细胞癌的进展。并用 Western blot 检测与 PI3K/AKT 信号通路相关的蛋白的表达。结果表明，VPS72 在肝细胞癌组织和细胞系中高表达，并与预后不良相关。VPS72 敲低抑制 HuH-7 细胞的增殖、侵袭和迁移。此外，VPS72 可以与 KAT5 结合。KAT5 的过表达逆转了 VPS72 敲低对 HuH-7 细胞增殖、侵袭和迁移的抑制作用。此外，VPS72 沉默下调了 p-PI3K 和 p-AKT 的表达，而过表达 KAT5 则恢复了这一表达。综上所述，VPS72 通过调节 PI3K/AKT 信号通路与 KAT5 结合促进肝细胞癌的进展。
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