【摘要】 目的以人胶质瘤放疗抵抗株M059K与放疗敏感株M059J为实验模型,筛选出与放疗抵抗相关的LncRNA TCONS₀0008552,并初步研究其对胶质瘤放疗抵抗、侵袭转移的影响。方法在M059K、M059J细胞中分别干扰和过表达TCONS₀0008552,通过MTT实验、平板克隆形成、划痕实验、Transwell侵袭实验,检测其对胶质瘤细胞增殖、放疗敏感性以及侵袭转移的影响。结果 MTT实验显示TCONS₀0008552可以增强胶质瘤细胞的增殖;划痕实验和Tanswell侵袭实验表明,该LncRNA增加胶质瘤细胞的迁移和侵袭能力;平板克隆形成实验和Western Blot结果显示,其可促进胶质瘤细胞的放疗抵抗,减轻放疗辐射诱导的细胞凋亡。结论 LncRNA TCONS₀0008552在胶质瘤放疗抵抗株中高表达,并促进肿瘤细胞的放疗抵抗、迁移和侵袭。更多还原

【Abstract】 Objective To investigate the potential role of LncRNAs in the progression of glioma, microarray analysis was used to assess differential expression of LncRNAs and mRNAs between M059 K and its parental cell line,M059 J,which is 30 times more sensitive to radiotherapy. Our results showed that the expression level of LncRNA TCONS₀0008552 was remarkably up-regulated in M059 K. And its roles on radiation sensitivity,migration and invasion in glioma were investigated in our study. Methods LncRNA TCONS₀0008552 was silenced in M059 K cells by siRNA and upregulated in M059 J by lentiviral vector. Their expressions were examined by RT-PCR.The effects on the proliferation and radio-sensitivity were observed by the MTT and colony formation assay,and the effects on the migration and invasion of glioma cells was observed by the wound healing and Transwell assay.Results The MTT assay showed that the downregulation of TCONS₀0008552 inhibited the proliferation of M059 K and its upregulation promoted the proliferation of M059 J. The colony formation assay revealed that TCONS₀0008552 deletion increased the radio-sensitivity of M059 K and TCONS₀0008552 overexpression decreased the radio-sensitivity of M059 J. The wound healing and Transwell assay showed that TCONS₀0008552 overexpression promoted the migration and invasion of glioma cells by upregulating EMT pathway. Conclusion Upregulation of TCONS₀0008552 enhanced the proliferation,radiation resistance,migration and invasion of glioma cells in vitro.更多还原