Inhibition of TDP43-Mediated SNHG12-miR-195-SOX5 Feedback Loop Impeded Malignant Biological Behaviors of Glioma Cells
发布时间 :2018-04-02
研究对象:SNHG12; 期刊:Molecular Therapy; 影响因子:5.660; 合作单位:中国医科大学; 发表时间:2018年3月



摘要:

Long non-coding RNA (lncRNA) dysregulation is involved in tumorigenesis and regulation of diverse cellular processes in gliomas. lncRNA SNHG12 is upregulated and promotes cell growth in human osteosarcoma cells. TAR-DNA binding protein 43 (TDP43) functions as an oncogene in various tumors by modulating RNA expression. Downregulation of TDP43 or SNHG12 significantly inhibited malignant biological behaviors of glioma cells. miR-195, downregulated in glioma tissues and cells, significantly impaired the malignant progression of glioma cells. TDP43 upregulated miR-195 in an SNHG12-dependent manner. We further revealed that SNHG12 and miR-195 were in an RNA-induced silencing complex (RISC). Inhibition of SNHG12 combined with restoration of miR-195 robustly reduced tumor growth in vivo. SOX5 was overexpressed in glioma tissues and cells. miR-195 targeted SOX5 3’UTR in a sequence-specific manner. Gelsolin was activated by SOX5. More importantly, SOX5 activated SNHG12 promoter and upregulated its expression, forming a feedback loop. Dysregulation of SNHG12, miR-195, and SOX5 predicted poor prognosis of glioma patients. The present study demonstrated that SNHG12-miR-195-SOX5 feedback loop exerted a crucial role in the regulation of glioma cells’ malignant progression.


KeywordsSNHG12, miR-195, SOX5, TDP43, gliomas


合作部分结果


伯信合作技术

LncRNA FISH探针


原文链接

https://doi.org/10.1016/j.omtn.2017.12.001.