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Abstract：
Hepatocellular carcinoma (HCC) is the sixth most common malignant tumors and the third leading cause of cancer-related death worldwide. As an oncogene, Rab23 has been shown to be significantly related to the growth and migration of hepatocellular carcinoma in both in vitro and in vivo studies, but its underlying mechanism remains obscure. In the present study, we examined the effect of inhibiting Rab23 expression on the pathological progression of HCC. The correlation between liver Rab23 gene expression and survival probability in human HCC patients was analyzed using the TCGA database and CPTAC database. Rab23 knockdown hepatocellular carcinoma cell line was generated through lentiviral transduction, then we established a nude HCC xenograft model by subcutaneously implanting the transfected cells. The analysis of gene and protein expression was carried out using Western blot or RT-qPCR, respectively. Flow cytometry analysis was used to detect the level of apoptosis. The expression levels of key proteins involved in the Sonic Hedgehog (SHH) signaling pathway were assessed. The results showed that HCC patients with low levels of hepatic Rab23 mRNA and protein had a better survival tendency than those with higher levels of Rab23. Cell proliferations were reduced and apoptosis levels were increased after Knocking down Rab23 in HCC cell lines. Furthermore, in vivo studies have demonstrated that suppression of the Rab23 gene results in decreased tumor size, proliferation rate, and reduced levels of SHH-related proteins Smoothened and GLI-1. The above results suggest that Rab23 is involved in the pathological progression of HCC as an important regulator of the SHH signaling pathway, which also provides an important research basis for new therapeutic strategies for HCC.
摘要：
肝细胞癌（HCC）是全球第六大最常见的恶性肿瘤，也是癌症相关死亡的第三大原因。作为一种致癌基因，在体外和体内研究中，Rab23已被证明与肝细胞癌的生长和迁移显着相关，但其潜在机制仍然模糊。在本研究中,我们研究了抑制Rab23表达对HCC病理进展的影响。使用TCGA数据库和CPTAC数据库分析了肝Rab23基因表达与人类HCC患者生存概率之间的相关性。通过慢病毒转导产生Rab23敲低肝癌细胞系，然后我们通过皮下植入转染的细胞建立了裸鼠肝癌异种移植模型。使用Westernblot或RT-qPCR进行基因和蛋白质表达的分析，分别。流式细胞仪检测细胞凋亡水平。评估了SonicHedgehog（SHH）信号通路中涉及的关键蛋白的表达水平。结果表明，肝脏Rab23mRNA和蛋白水平较低的HCC患者比Rab23水平较高的HCC患者具有更好的生存趋势。在HCC细胞系中敲除Rab23后，细胞增殖减少，凋亡水平增加。此外，体内研究表明，抑制Rab23基因导致肿瘤大小减小，增殖率,SHH相关蛋白Smoothened和GLI-1的水平降低。以上结果提示Rab23作为SHH信号通路的重要调节因子参与HCC的病理进程,为HCC新的治疗策略提供了重要的研究基础。
