Zhang Shi-Zhe, Zhu Xiao-Dong, Feng Long-Hai, Li Xiao-Long, Liu Xue-Feng, Sun Hui-Chuan, Tang Zhao-You
Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, 200032, China.
Exp Hematol Oncol. 2021 Mar 31;10(1):25. doi: 10.1186/s40164-021-00218-1.
Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key enzymes in the process of lipid transport, is involved in the disease progression of various types of tumors. This article is to study the role of PCSK9 in the progression of hepatocellular carcinoma (HCC).
Immunohistochemistry was used to assess the expression of PCSK9 in tumor specimens from 105 HCC patients who underwent curative resection. Western blotting and quantitative real-time PCR were used to test the protein and mRNA expression levels in HCC cell lines. Cell Counting Kit-8 (CCK-8) and clone formation assays were performed to evaluate the proliferation ability of different kinds of cells in vitro. Flow cytometry was used to analyze cell cycle distribution and apoptosis rate. A xenograft model was established to study the effect of PCSK9 on HCC growth in vivo. TUNEL and immunofluorescence assays were used to detect cell apoptosis.
High expression of PCSK9 in tumor tissues was related to microvascular invasion (p = 0.036) and large tumor size (p = 0.001) in HCC patients. Overall survival and disease-free survival after surgery were poor in patients with high expression of PCSK9 (p = 0.035 and p = 0.007, respectively). In vivo and in vitro experiments showed that PCSK9 promoted the growth of HCC by inhibiting cell apoptosis. A mechanistic study revealed that PCSK9 increases FASN expression, thereby inhibiting apoptosis of HCC cells via the Bax/Bcl-2/Caspase9/Caspase3 pathway.
PCSK9 expression level in HCC is an indicator of poor prognosis for patients with HCC. FASN-mediated anti-apoptosis plays an important role in PCSK9-induced HCC progression.
前蛋白转化酶枯草溶菌素/克新9型（PCSK9）是脂质运输过程中的关键酶之一，参与多种类型肿瘤的疾病进展。本文旨在研究PCSK9在肝细胞癌（HCC）进展中的作用。
采用免疫组织化学法评估105例行根治性切除的HCC患者肿瘤标本中PCSK9的表达。采用蛋白质印迹法和定量实时聚合酶链反应检测HCC细胞系中的蛋白质和mRNA表达水平。进行细胞计数试剂盒-8（CCK-8）和克隆形成试验以评估不同类型细胞在体外的增殖能力。采用流式细胞术分析细胞周期分布和凋亡率。建立异种移植模型以研究PCSK9对HCC体内生长的影响。采用末端脱氧核苷酸转移酶介导的缺口末端标记法（TUNEL）和免疫荧光试验检测细胞凋亡。
肿瘤组织中PCSK9的高表达与HCC患者的微血管侵犯（p = 0.036）和肿瘤体积较大（p = 0.001）相关。PCSK9高表达患者术后的总生存期和无病生存期较差（分别为p = 0.035和p = 0.007）。体内和体外实验表明，PCSK9通过抑制细胞凋亡促进HCC的生长。机制研究显示，PCSK9增加脂肪酸合酶（FASN）的表达，从而通过Bax/Bcl-2/Caspase9/Caspase3途径抑制HCC细胞的凋亡。
HCC中PCSK9的表达水平是HCC患者预后不良的一个指标。FASN介导的抗凋亡在PCSK9诱导的HCC进展中起重要作用。
