Inhibition of TDP43-Mediated SNHG12-miR-195-SOX5 Feedback Loop Impeded Malignant Biological Behaviors of Glioma Cells

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 modulat...

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Published in:Molecular therapy. Nucleic acids 2018-03, Vol.10, p.142-158
Main Authors: Liu, Xiaobai, Zheng, Jian, Xue, Yixue, Qu, Chengbin, Chen, Jiajia, Wang, Zhenhua, Li, Zhen, Zhang, Lei, Liu, Yunhui
Format: Article
Language:English
Subjects:
Apoptosis
Binding sites
Bone cancer
Brain cancer
Brain tumors
Breast cancer
Cancer therapies
Cell growth
Conflicts of interest
Data analysis
Experiments
Feedback
feedback loop
Gelsolin
Gene expression
Glioma
Glioma cells
MicroRNAs
miR-195
Non-coding RNA
Osteosarcoma
Osteosarcoma cells
RNA-induced silencing complex
RNA-mediated interference
Roles
Sarcoma
SNHG12
Software
SOX5
TDP43
Tumorigenesis
Tumors
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Summary: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.
ISSN:2162-2531
2162-2531
DOI:10.1016/j.omtn.2017.12.001