【摘要】 目的 探究长链非编码RNA人肺腺癌转移相关转录本1(metastasis-associated lung adenocarcinoma transcript 1,MALAT1)对骨肉瘤细胞系MG63及U2OS增殖和迁移的影响及其机制。方法 运用GEO数据库对差异表达的LncRNA基因进行筛选及生存分析；CCK-8法、细胞划痕实验检测MALAT1受抑制后对骨肉瘤细胞增殖和迁移的影响；流式细胞仪检测细胞周期及凋亡的变化；RT-qPCR和Western blot检测MALAT1受抑制后对凋亡相关基因mRNA和蛋白水平的影响。结果GEO数据库进行生信分析发现，骨肉瘤中共有536个基因表达水平表达异常，其中MALAT1与骨肉瘤患者生存密切相关。细胞实验发现，MALAT1在骨肉瘤细胞系表达升高，敲除MALAT1后，骨肉瘤细胞的增殖和迁移能力下降。同时，敲除MALAT1能促进凋亡相关蛋白Caspase3的表达，抑制SphK1和p-mTOR的表达，并降低p-mTOR/mTOR比例。结论 LncRNA MALAT1能抑制细胞凋亡，并促进骨肉瘤细胞的增殖和迁移，与骨肉瘤患者的生存预后密切相关，可作为骨肉瘤靶向治疗的潜在生物靶点。更多还原

【Abstract】 Objective To investigate the effect of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1(MALAT1) on the proliferation and migration of osteosarcoma cell lines MG63 and U2OS. Methods The differentially expressed LncRNA genes were screened and analyzed by GEO database; CCK-8 and scratch test were used to detect the effect of MALAT1 on the proliferation and migration of osteosarcoma cells; Cell cycle and apoptosis were detected by flow cytometry; RT-qPCR and Western blot were used to detect the mRNA and protein levels of apoptosis related genes. Results GEO database analysis revealed 536 genes abnormally expressed in osteosarcoma, and MALAT1 was found closely related to the survival of osteosarcoma patients. Cell experiments showed that the expression of MALAT1 was increased in osteosarcoma cell lines, and the proliferation and migration ability of osteosarcoma cells were decreased after knockout of MALAT1. In addition, knockout of MALAT1 could promote the expression of Caspase3, inhibit the expression of SphK1 and p-mTOR, and reduce the ratio of p-mTOR/mTOR. Conclusion Lnc RNA MALAT1 can inhibit cell apoptosis and promote the proliferation and migration of osteosarcoma cells, which is closely related to the survival and prognosis of osteosarcoma patients, and could serve as a potential biological target for targeted therapy of osteosarcoma.更多还原