基于TGF-β通路考察BMP4/FBN1对脊髓室管膜瘤增殖侵袭性的影响  

Effects of BMP4/FBN1 on the proliferation and invasiveness of spinal cord ependymoma based on TGF⁃βpathway

作　　者：范雁东 朱曼丽 邓国棋 王佳明[3] 罗坤 FAN Yan-dong;ZHU Man-i;DENG Guo-qi;WANG Jia-ming;LUO Kun(Neurosurgery Department of the Second Affiliated Hospital of Xinjiang Medical University,830000;Central Laboratory of Xinjiang Medical University,830000;Neurosurgery Department of the First Affiliated Hospital of Xinjiang Medical University,830054)

机构地区：[1]新疆医科大学第二附属医院神经外科,新疆乌鲁木齐830000 [2]新疆医科大学中心实验室,新疆乌鲁木齐830000 [3]新疆医科大学第一附属医院神经外科,新疆乌鲁木齐830054

出　　处：《解剖学研究》2024年第3期216-220,227,共6页Anatomy Research

基　　金：省部共建中亚高发病成因与防治国家重点实验室开放课题项目(SKL⁃HIDCA⁃2022⁃NKX2)。

摘　　要：目的基于TGF-β通路考察BMP4/FBN1对脊髓室管膜瘤(SCE)增殖侵袭性的影响及其相关机制。方法收集SCE患者肿瘤组织,同时收集正常组织作为对照,分为对照组、病例组。利用SCE患者肿瘤组织培养肿瘤细胞,并用携带FBN1 shRNA,BMP4 shRNA的慢病毒基因敲除FBN1或BMP4蛋白的表达。通过qRT-PCR和Western Blot检测肿瘤组织样本中FBN1和BMP4基因和蛋白表达水平。在BMP4低表达和FBN1低表达肿瘤细胞中通过qRT-PCR检测TGF-β基因表达水平;同时通过CCK-8细胞增殖实验与Transwell侵袭实验进一步检测敲低FBN1或BMP4蛋白的表达对肿瘤细胞增殖和侵袭能力的影响。结果与对照组相比,病例组BMP4和FBN1基因表达量升高(分别为P<0.05,P<0.01),蛋白表达量也升高(P<0.01);敲低FBN或BMP4蛋白不仅可下调SCE细胞中TGF-β基因的表达(分别为P<0.05、P<0.01),同时抑制了SCE细胞的增殖与侵袭能力(分别为P<0.05、P<0.01)。结论本研究基于TGF-β通路,考察关键分子BMP4/FBN1对SCE增殖侵袭性的影响,提示FBN1、BMP4与TGF-β之间可能存在相互作用,为临床治疗罕见病SCE提供可用的理论基础。Objective To investigate the effect of BMP4/FBN1 on the proliferation and invasiveness of spinal cord ependymoma(SCE)based on TGF⁃βpathway.Methods Tumor tissues and normal tissues of SCE pa⁃tients were collected and divided into control group and case group.Cancer cells were cultured from SCE patients and the expression of FBN1 or BMP4 protein was knocked down with lentivirus gene carrying FBN1 shRNA and BMP4 shRNA.The expression levels of FBN1 and BMP4 genes and proteins in tumor tissue samples were detected by qRT⁃PCR and Western blot.The expression level of TGF⁃βgene was detected by qRT⁃PCR in tumor cells with low expression of BMP4 and FBN1.Effects of FBN1 or BMP4 protein knockdown in cancer cells on the proliferation and invasion were further examined by CCK⁃8 cell proliferation assay and Transwell invasion assay.Results Com⁃pared with the control group,BMP4 and FBN1 gene expression(P<0.05,P<0.01,respectively),and protein expres⁃sion were also significantly increased in the case group(P<0.01).Knockdown of FBN or BMP4 protein not only down⁃regulated the expression of TGF⁃βgene in SCE cells(P<0.05,P<0.01,respectively),but also inhibited the prolifer⁃ation and invasion ability of SCE cells(P<0.05,P<0.01,respectively).Conclusion Based on TGF⁃βpathway,this study investigated the influence of BMP4/FBN1 on the proliferation and invasiveness of SCE,suggesting that there may be interactions between FBN1,BMP4 and TGF⁃β.Here we provided a useful theoretical basis for clinical treat⁃ment of SCE.

关 键 词：脊髓室管膜瘤 转化生长因子-Β 骨形态发生蛋白-4 原纤维蛋白1 增殖 侵袭 

分 类 号：R739.42[医药卫生—肿瘤]