Mol Ther Nucleic Acids
2018 Mar 2:10:142-158.
doi: 10.1016/j.omtn.2017.12.001. Epub 2017 Dec 8.
Inhibition of TDP43-Mediated SNHG12-miR-195-SOX5 Feedback Loop Impeded Malignant Biological Behaviors of Glioma Cells
Xiaobai Liu 1, Jian Zheng 1, Yixue Xue 2, Chengbin Qu 1, Jiajia Chen 2, Zhenhua Wang 3, Zhen Li 1, Lei Zhang 1, Yunhui Liu 4
Affiliations expand
PMID: 29499929
PMCID: PMC5751968
DOI: 10.1016/j.omtn.2017.12.001
Abstract
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.
Keywords: SNHG12; SOX5; TDP43; feedback loop; glioma; miR-195.
参考连接：
https://pubpeer.com/publications/734D1E8C4A28DECFDD81E9A90C2E14
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