BACKGROUND Spindle and kinetochore-associated complex subunit 3(SKA3)is a malignancyassociated gene that plays a critical role in the regulation of chromosome separation and cell division.However,the molecular mechani...BACKGROUND Spindle and kinetochore-associated complex subunit 3(SKA3)is a malignancyassociated gene that plays a critical role in the regulation of chromosome separation and cell division.However,the molecular mechanism through which SKA3 regulates tumor cell proliferation in hepatocellular carcinoma(HCC)has not been fully elucidated.AIM To investigate the molecular mechanisms underlying the role of SKA3 in HCC.METHODS SKA3 expression,clinicopathological,and survival analyses were performed using multiple public database platforms,and the results were verified by Western blot and immunohistochemistry staining using collected clinical samples.Functional enrichment analyses were performed to evaluate the biological functions and molecular mechanisms of SKA3 in HCC.Furthermore,the Tumor Immune Estimation Resource and single-sample Gene Set Enrichment Analysis(ssGSEA)algorithms were utilized to investigate the abundance of tumor-infiltrating immune cells in HCC.The response to chemotherapeutic drugs was evaluated by the R package“pRRophetic”.RESULTS We found that upregulated SKA3 expression was significantly correlated with poor prognosis in patients with HCC.Multivariable Cox regression analysis indicated that SKA3 was an independent risk factor for survival.GSEA revealed that SKA3 expression may facilitate proliferation and migratory processes by regulating the cell cycle and DNA repair.Moreover,patients with high SKA3 expression had significantly decreased ratios of CD8+T cells,natural killer cells,and dendritic cells.Drug sensitivity analysis showed that the high SKA3 group was more sensitive to sorafenib,sunitinib,paclitaxel,doxorubicin,gemcitabine,and vx-680.CONCLUSION High SKA3 expression led to poor prognosis in patients with HCC by enhancing HCC proliferation and repressing immune cell infiltration surrounding HCC.SKA3 may be used as a biomarker for poor prognosis and as a therapeutic target in HCC.展开更多
目的研究癌基因纺锤体与着丝粒相关蛋白3(spindle and kinetochore-associated proteins 3,SKA3)在非小细胞肺癌中的表达规律及作用调控机制。方法选取山东省公共卫生临床中心病理科2019年1—12月检验的60例非小细胞肺癌组织蜡块作为观...目的研究癌基因纺锤体与着丝粒相关蛋白3(spindle and kinetochore-associated proteins 3,SKA3)在非小细胞肺癌中的表达规律及作用调控机制。方法选取山东省公共卫生临床中心病理科2019年1—12月检验的60例非小细胞肺癌组织蜡块作为观察组,同时随机选取30例癌旁正常肺组织作为对照组,制作非小细胞肺癌组织片。利用免疫细胞化学法(immunohistochemistry,IHC)检测SKA3在非小细胞肺癌及癌旁正常肺组织中的表达情况。以非小细胞肺癌细胞系两步A549及SK-MES-1为体外研究模型,用平板克隆实验、Transwell侵袭实验、流式细胞术分别检测敲低SKA3对非小细胞肺癌细胞增殖能力、侵袭能力及凋亡能力的影响。结果免疫组化技术显示SKA3在非小细胞肺癌组织中的阳性表达率明显高于癌旁正常肺组织(68.3%vs 16.6%),差异有统计学意义(χ^(2)=18.678,P<0.05),平板克隆试验显示脂质体转染siRNA细胞株敲低SKA3表达后观察癌细胞克隆数为(11±2)个,明显少于对照组的(97±11)个,差异有统计学意义(t=-652.977,P<0.05),流式细胞仪检测显示脂质体转染干扰组细胞G1/G0期和S期细胞比率分别为(71.7±6.1)%和(20.2±2.9)%,对照组相应为(53.4±5.4)%和(31.3±4.2)%,两组比较差异有统计学意义(t=13.922、-14.669,P<0.05)。结论SKA3在肺癌中高表达,可促进肺癌细胞增殖及侵蚀,有希望成为非小细胞肺癌的预防和治疗靶点。展开更多
基金Beijing Hope Run Special Fund of Cancer Foundation of China,No.LC2020L05.
文摘BACKGROUND Spindle and kinetochore-associated complex subunit 3(SKA3)is a malignancyassociated gene that plays a critical role in the regulation of chromosome separation and cell division.However,the molecular mechanism through which SKA3 regulates tumor cell proliferation in hepatocellular carcinoma(HCC)has not been fully elucidated.AIM To investigate the molecular mechanisms underlying the role of SKA3 in HCC.METHODS SKA3 expression,clinicopathological,and survival analyses were performed using multiple public database platforms,and the results were verified by Western blot and immunohistochemistry staining using collected clinical samples.Functional enrichment analyses were performed to evaluate the biological functions and molecular mechanisms of SKA3 in HCC.Furthermore,the Tumor Immune Estimation Resource and single-sample Gene Set Enrichment Analysis(ssGSEA)algorithms were utilized to investigate the abundance of tumor-infiltrating immune cells in HCC.The response to chemotherapeutic drugs was evaluated by the R package“pRRophetic”.RESULTS We found that upregulated SKA3 expression was significantly correlated with poor prognosis in patients with HCC.Multivariable Cox regression analysis indicated that SKA3 was an independent risk factor for survival.GSEA revealed that SKA3 expression may facilitate proliferation and migratory processes by regulating the cell cycle and DNA repair.Moreover,patients with high SKA3 expression had significantly decreased ratios of CD8+T cells,natural killer cells,and dendritic cells.Drug sensitivity analysis showed that the high SKA3 group was more sensitive to sorafenib,sunitinib,paclitaxel,doxorubicin,gemcitabine,and vx-680.CONCLUSION High SKA3 expression led to poor prognosis in patients with HCC by enhancing HCC proliferation and repressing immune cell infiltration surrounding HCC.SKA3 may be used as a biomarker for poor prognosis and as a therapeutic target in HCC.
