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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.

Author information

1
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang 110004, China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, China.
2
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, China; Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110122, China; Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, China.
3
Department of Physiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning 110122, China.
4
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang 110004, China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, China. Electronic address: liuyh_cmuns@163.com.

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

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