[1]凌峰,张勇,辛向阳.纺锤体动粒相关复合体-1（SKA1）促进葡萄膜黑色素瘤细胞增殖的分子机制研究[J].眼科新进展,2021,41(8):727-731.[doi:10.13389/j.cnki.rao.2021.0151]
　LING Feng,ZHANG Yong,XIN Xiangyang.Molecular mechanism of spindle and kinetochore associated complex-1 in promoting the proliferation of uveal melanoma cells[J].Recent Advances in Ophthalmology,2021,41(8):727-731.[doi:10.13389/j.cnki.rao.2021.0151]
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纺锤体动粒相关复合体-1（SKA1）促进葡萄膜黑色素瘤细胞增殖的分子机制研究/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
41卷
期数:
2021年8期
页码:
727-731
栏目:
实验研究
出版日期:
2021-08-05

文章信息/Info

Title:
Molecular mechanism of spindle and kinetochore associated complex-1 in promoting the proliferation of uveal melanoma cells
作者:
凌峰; 张勇; 辛向阳
014010　内蒙古自治区包头市，内蒙古医科大学第三附属医院（内蒙古包钢医院）眼科(凌峰，辛向阳)；010000　内蒙古自治区呼和浩特市，内蒙古自治区人民医院肿瘤科(张勇)
Author(s):
LING Feng1;  ZHANG Yong2;  XIN Xiangyang1
1.Department of Ophthalmology, the Third Affiliated Hospital of Inner Mongolia Medical University (Inner Mongolia Baogang Hospital), Baotou 014010, Inner Mongolia Autonomous Region, China
2.Department of Oncology, Inner Mongolia Autonomous Region People’s Hospital, Huhehaote 010000, Inner Mongolia Autonomous Region, China
关键词:
纺锤体动粒相关复合体-1; 葡萄膜黑色素瘤; 胰岛素样生长因子结合蛋白-3; 细胞增殖; 细胞凋亡
Keywords:
spindle and kinetochore associated complex-1;  uveal melanoma;  insulin-like growth factor-binding protein-3;  cell proliferation;  cell apoptosis
分类号:
R773
DOI:
10.13389/j.cnki.rao.2021.0151
文献标志码:
A
摘要:
目的　研究纺锤体动粒相关复合体-1（SKA1）促进葡萄膜黑色素瘤（UM）细胞增殖的分子机制。方法　利用SKA1敲减及空载体慢病毒感染MUM-2B细胞分别作为SKA1敲减组和对照组，再以MTT法、流式细胞术及Caspase-3/7法检测各组细胞增殖、凋亡表型的变化；利用基因表达谱芯片筛选差异基因，KEGG富集分析探寻SKA1促进UM发生发展的潜在信号通路，再以Western blot检测信号通路中关键蛋白的表达变化；利用TCGA数据库UM样本RNA测序及随访数据，分析SKA1表达与预后的关系。结果　与对照组相比，SKA1敲减组细胞培养3 d、4 d、5 d的光密度均显著降低（均为P<0.01），而凋亡细胞比例及Caspase-3/7活性均显著增加（均为P<0.01）。KEGG富集分析显示，差异基因富集于P53信号通路。Western blot检测结果证实，SKA1敲减后，P53通路中胰岛素样生长因子结合蛋白-3(IGFBP3)的表达显著下降（P<0.05）。SKA1高表达患者总生存率下降（P=0.021,HR=2.55,95%CI:0.92~7.05）。结论　SKA1通过P53/IGFBP3信号通路促进UM细胞增殖，而且SKA1高表达是影响UM患者预后的危险因素。
Abstract:
Objective　To investigate the molecular mechanism of spindle and kinetochore associated complex-1 (SKA1) in promoting uveal melanoma (UM) cell proliferation.Methods　MUM-2B cells were infected by lentivirus through SKA1 knockdown (SKA1 group) and empty vector (control group). Cell proliferation and apoptotic phenotype were detected by MTT assay, flow cytometry and Caspase-3/7 assay. Gene expression microarray was used to screen differential genes, KEGG enrichment analysis was performed to explore the potential signaling pathways through which SKA1 promotes the development of UM, and Western blot was used to detect the changes of key proteins in the signaling pathways. The relationship between SKA1 expression and prognosis was analyzed using UM RNA-Seq and follow-up data from TCGA database.Results　Compared with the control group, the optical density of the SKA1 group was significantly reduced at day 3, 4 and 5 after the cell culture (all P<0.01), while the cell apoptosis rate and Caspase-3/7 activity were significantly increased (all P<0.01). KEGG enrichment analysis results showed that the differential genes were enriched in the P53 signaling pathway. Western blot confirmed that the expression of insulin-like growth factor-binding protein-3 (IGFBP-3) in the P53 pathway was significantly decreased after SKA1 knockdown (P<0.05). The overall survival of patients with high SKA1 expression decreased (P=0.021, HR=2.55, 95% CI: 0.92-7.05).Conclusion　SKA1 promotes the proliferation of UM cells through the P53/IGFBP-3 signaling pathway, and the high SKA1 expression is a risk factor for the prognosis of UM patients.

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备注/Memo

备注/Memo:
内蒙古自治区自然科学基金资助（编号：2020MS08094）
更新日期/Last Update: 2021-08-05