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.

长期的非编码RNA（lncRNA）失调与神经胶质瘤的肿瘤发生和多种细胞过程的调控有关。lncRNA SNHG12被上调并促进人骨肉瘤细胞中的细胞生长。TAR-DNA结合蛋白43（TDP43）通过调节RNA表达在各种肿瘤中起癌基因的作用。TDP43或SNHG12的下调显着抑制神经胶质瘤细胞的恶性生物学行为。在神经胶质瘤组织和细胞中下调的miR-195显着损害神经胶质瘤细胞的恶性进展。TDP43以SNHG12依赖性方式上调miR-195。我们进一步揭示了SNHG12和miR-195在RNA诱导的沉默复合体（RISC）中。SNHG12的抑制与miR-195的恢复相结合，可显着降低体内肿瘤的生长。SOX5在神经胶质瘤组织和细胞中过表达。miR-195以序列特异性方式靶向SOX5 3'UTR。凝溶胶蛋白被SOX5激活。更重要的是，SOX5激活了SNHG12启动子并上调了它的表达，形成了一个反馈环。SNHG12，miR-195和SOX5的失调预示了神经胶质瘤患者的不良预后。本研究表明，SNHG12-miR-195-SOX5反馈回路在胶质瘤细胞恶性进展的调节中起着至关重要的作用。