Zhou Bin, Chen Tian-Wei, Jiang Ya-Bo, Wei Xu-Biao, Lu Chong-De, Li Jing-Jing, Xie Dong, Cheng Shu-Qun
Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
Oncol Lett. 2020 Mar;19(3):2011-2020. doi: 10.3892/ol.2020.11262. Epub 2020 Jan 8.
Hepatocellular carcinoma (HCC) remains an intractable disease despite numerous advancements made in the available treatments over recent decades. Therefore, investigation of the underlying pathogenesis of HCC is urgently required. Our previous microarray result showed that SCIN was generally downregulated in 23 paired tumor/normal tissues. Reverse transcription-quantitative PCR, western blotting and immunohistochemistry were performed in the present study in order to detect the expression of scinderin (SCIN). Lentivirus-mediated gene delivery was used in order to produce SCIN-manipulated cell lines. MTT and crystal violet assays were performed in order to investigate cell growth, and fluorescence-activated cell sorting analysis was used in order to determine cell cycle distribution. SCIN was downregulated in HCC samples, and low SCIN expression predicted the poor prognosis of patients with HCC. Notably, SCIN may have the potential to serve as an independent risk factor for overall survival (3-year overall survival rate of 28.6 and 10.3% in high SCIN expression and low SCIN expression groups, respectively) and disease-free survival (3-year recurrence rate of 71.4 and 84.6% in high SCIN expression and low SCIN expression groups, respectively) in HCC. SCIN inhibited HCC cell proliferation both and in subcutaneous tumor formation assay. Furthermore, SCIN decreased the levels of phosphorylated STAT3, thereby downregulating cyclin A1 levels in HCC cells. The results of the present study demonstrate the tumor suppressive role of SCIN in HCC, providing a candidate strategy to treat this disease.
尽管近几十年来现有治疗方法取得了诸多进展，但肝细胞癌（HCC）仍然是一种难以治疗的疾病。因此，迫切需要对HCC的潜在发病机制进行研究。我们之前的微阵列结果显示，在23对肿瘤/正常组织中，SCIN普遍下调。在本研究中进行了逆转录定量PCR、蛋白质印迹和免疫组织化学，以检测scinderin（SCIN）的表达。使用慢病毒介导的基因传递来构建SCIN调控的细胞系。进行MTT和结晶紫试验以研究细胞生长，并使用荧光激活细胞分选分析来确定细胞周期分布。SCIN在HCC样本中下调，低SCIN表达预示着HCC患者的预后不良。值得注意的是，SCIN可能有潜力作为HCC总生存期（高SCIN表达组和低SCIN表达组的3年总生存率分别为28.6%和10.3%）和无病生存期（高SCIN表达组和低SCIN表达组的3年复发率分别为71.4%和84.6%）的独立危险因素。SCIN在体外和皮下肿瘤形成试验中均抑制HCC细胞增殖。此外，SCIN降低了磷酸化STAT3的水平，从而下调了HCC细胞中细胞周期蛋白A1的水平。本研究结果证明了SCIN在HCC中的肿瘤抑制作用，为治疗该疾病提供了一种候选策略。
