Spindle and kinetochore-related complex subunit 3 (SKA3) is a component of the spindle and kinetochore-related complexes and is essential for accurate timing of late mitosis. However, the relationship between SKA3 and hepatocellular carcinoma (HCC) has not yet been fully elucidated. Gene expression omnibus (GEO) (GSE62232, GSE45436, GSE6764, and GSE36376) and The Cancer Atlas (TCGA) datasets were analyzed to identify differential expression genes. Cell proliferation ability was analyzed using Cell Counting Kit-8 (CCK8) assay and plate clone formation assay, while scratch wound healing assay and transwell assay were used to analyze cell invasion. The role of SKA3 in vivo was explored using subcutaneous xenotransplantation model and lung metastasis model. Bioinformatics analysis found that hepatocellular carcinoma patients with high levels of expression of SKA3 have a poor prognosis. Similarly, immunohistochemical staining of 236 samples of tumors also found higher SKA3 expression in them, than in adjacent normal liver tissues. Significant levels of inhibition of in vivo and in vitro tumor proliferation and invasion result from the downregulation of SKA3. Mechanistically, SKA3 was found to affect tumor progression through the cell cycle and P53 signaling pathway as shown by the gene enrichment analysis (GSEA). G2/M phase arrest and severe apoptosis was also found to result from SKA3 knockdown, as shown by the inhibition of CDK2/p53 phosphorylation together with downregulation of BAX/Bcl-2 expression in HCC cells. Overall, these findings uncover the role of SKA3 in regulating the apoptosis and proliferation of hepatocellular carcinoma cells. This study was able to uncover new information on the tumorigenesis mechanism in hepatocellular carcinoma.

中文翻译：

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SKA3通过调节肝细胞癌CDK2 / P53磷酸化来促进肿瘤生长。

纺锤体和线粒体相关复合物亚基3（SKA3）是纺锤体和线粒体相关复合物的组成部分，对于后期有丝分裂的准确计时至关重要。但是，尚未完全阐明SKA3与肝细胞癌（HCC）之间的关系。对基因表达综合（GEO）（GSE62232，GSE45436，GSE6764和GSE36376）和《癌症图集》（TCGA）数据集进行了分析，以鉴定差异表达基因。使用细胞计数试剂盒8（CCK8）分析和板克隆形成分析来分析细胞增殖能力，而使用划痕伤口愈合分析和transwell分析来分析细胞侵袭。使用皮下异种移植模型和肺转移模型探讨了SKA3在体内的作用。生物信息学分析发现，SKA3高表达的肝细胞癌患者预后较差。同样，对236个肿瘤样品的免疫组织化学染色也发现，与相邻的正常肝组织相比，它们中的SKA3表达更高。SKA3的下调导致体内和体外肿瘤增殖和侵袭的显着抑制水平。从机制上讲，如基因富集分析（GSEA）所示，发现SKA3通过细胞周期和P53信号通路影响肿瘤进展。还发现由SKA3敲低导致G2 / M期停滞和严重的凋亡，如抑制CDK2 / p53磷酸化以及下调HCC细胞中BAX / Bcl-2表达所表明的。全面的，这些发现揭示了SKA3在调节肝癌细胞凋亡和增殖中的作用。这项研究能够发现有关肝细胞癌发生机制的新信息。