LukS-PV Inhibits Hepatocellular Carcinoma Cells Migration via the TNNC1/PI3K/AKT Axis.
LukS-PV Inhibits Hepatocellular Carcinoma Cells Migration via the TNNC1/PI3K/AKT Axis.
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DOI：
10.2147/ott.s278540
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发表时间：
2020
影响因子：
4
通讯作者：
Ma X
中科院分区：
文献类型：
--
作者：
Ma F;Wang Z;Qiang Y;Xu L;Ding P;Wang Y;Ma X
肝细胞癌（Hepatocellular carcinoma，HCC）是世界范围内最常见的恶性肿瘤之一。LukS-PV是Panton-Valentine杀白细胞素（PVL）的S组分，PVL是由金黄色葡萄球菌分泌的毒素。我们的目的是研究LukS-PV在肝癌细胞迁移中的作用及其具体的分子机制。我们使用划痕试验来检测用LukS-PV处理的肝癌细胞的迁移率。采用实时荧光定量PCR和Western blot方法检测相关基因的表达水平。RNA测序和定量蛋白质组学测序用于评估靶基因的转录和蛋白质组学改变。RNA测序和京都基因和基因组百科全书（KEGG）以及基因集富集分析（GSEA）途径分析揭示了LukS-PV的下游信号传导途径靶标。我们的研究结果表明，LukS-PV可以抑制肝癌细胞的迁移，在浓度依赖性的方式。LukS-PV还能下调肝癌细胞中高表达的TNNC 1的表达。此外，研究表明LukS-PV通过下调TNNC 1抑制HCC细胞迁移。进一步研究表明LukS-PV通过靶向TNNC 1抑制PI 3 K/AKT通路的磷酸化，从而抑制肝癌细胞迁移。我们的研究表明LukS-PV对肝癌细胞通过TNNC 1/PI 3 K/AKT轴的迁移具有抑制作用。
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. LukS-PV is the S component of Panton-Valentine leucocidin (PVL), a toxin secreted by Staphylococcus aureus. We aimed to investigate the role of LukS-PV in HCC cell migration and the specific molecular mechanism involved. We used scratch assays to detect the mobility of liver cancer cells treated with LukS-PV. Quantitative real-time PCR and Western blot analysis were performed to detect the expression levels of related genes. RNA sequencing and quantitative proteomics sequencing were used to assess the transcriptional and proteomic alterations of target genes. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) pathway analyses revealed the downstream signaling pathway targets of LukS-PV. Our results demonstrated that LukS-PV could inhibit HCC cell migration in a concentration-dependent manner. LukS-PV could also downregulate the expression of TNNC1, which was highly expressed in HCC cells. Additionally, the study showed that LukS-PV inhibited HCC cell migration by downregulating TNNC1. Further studies showed that LukS-PV inhibited the phosphorylation of PI3K/AKT pathway by targeting TNNC1, thereby inhibiting HCC cell migration. Our study demonstrated that LukS-PV has an inhibitory role in the migration of liver cancer cells through the TNNC1/PI3K/AKT axis.