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BACKGROUND

Accumulating evidence has highlighted the potential role of long non-coding RNAs (lncRNAs) in the biological behaviors of glioblastoma stem cells (GSCs). Here, we elucidated the function and possible molecular mechanisms of the effect of lncRNA-SOX2OT on the biological behaviors of GSCs.

RESULTS

Real-time PCR demonstrated that SOX2OT expression was up-regulated in glioma tissues and GSCs. Knockdown of SOX2OT inhibited the proliferation, migration and invasion of GSCs, and promoted GSCs apoptosis. MiR-194-5p and miR-122 were down-regulated in human glioma tissues and GSCs, and miR-194-5p and miR-122 respectively exerted tumor-suppressive functions by inhibiting the proliferation, migration and invasion of GSCs, while promoting GSCs apoptosis. Knockdown of SOX2OT significantly increased the expression of miR-194-5p and miR-122 in GSCs. Dual-luciferase reporter assay revealed that SOX2OT bound to both miR-194-5p and miR-122. SOX3 and TDGF-1 were up-regulated in human glioma tissues and GSCs. Knockdown of SOX3 inhibited the proliferation, migration and invasion of GSCs, promoted GSCs apoptosis, and decreased TDGF-1 mRNA and protein expression through direct binding to the TDGF-1 promoter. Over-expression of miR-194-5p and miR-122 decreased the mRNA and protein expression of SOX3 by targeting its 3'UTR. Knockdown of TDGF-1 inhibited the proliferation, migration and invasion of GSCs, promoted GSCs apoptosis, and inhibited the JAK/STAT signaling pathway. Furthermore, SOX3 knockdown also inhibited the SOX2OT expression through direct binding to the SOX2OT promoter and formed a positive feedback loop.

CONCLUSION

This study is the first to demonstrate that the SOX2OT-miR-194-5p/miR-122-SOX3-TDGF-1 pathway forms a positive feedback loop and regulates the biological behaviors of GSCs, and these findings might provide a novel strategy for glioma treatment.

BACKGROUND

RESULTS

CONCLUSION

背景

越来越多的证据表明长链非编码 RNA（lncRNA）在神经胶质瘤干细胞（GSCs）的生物学行为中发挥着潜在作用。在这里，我们阐述了 lncRNA-SOX2OT 对 GSCs 生物学行为的影响的功能和可能的分子机制。

结果

实时 PCR 表明，SOX2OT 在神经胶质瘤组织和 GSCs 中表达上调。SOX2OT 敲低抑制 GSCs 的增殖、迁移和侵袭，并促进 GSCs 凋亡。miR-194-5p 和 miR-122 在人神经胶质瘤组织和 GSCs 中下调，miR-194-5p 和 miR-122 分别通过抑制 GSCs 的增殖、迁移和侵袭，促进 GSCs 凋亡，发挥肿瘤抑制作用。SOX2OT 敲低显著增加了 GSCs 中 miR-194-5p 和 miR-122 的表达。双荧光素酶报告基因实验显示，SOX2OT 与 miR-194-5p 和 miR-122 结合。SOX3 和 TDGF-1 在人神经胶质瘤组织和 GSCs 中上调。SOX3 敲低抑制 GSCs 的增殖、迁移和侵袭，促进 GSCs 凋亡，并通过直接结合 TDGF-1 启动子降低 TDGF-1 mRNA 和蛋白表达。miR-194-5p 和 miR-122 的过表达通过靶向其 3'UTR 降低 SOX3 的 mRNA 和蛋白表达。TDGF-1 敲低抑制 GSCs 的增殖、迁移和侵袭，促进 GSCs 凋亡，并抑制 JAK/STAT 信号通路。此外，SOX3 敲低还通过直接结合 SOX2OT 启动子抑制 SOX2OT 的表达，并形成正反馈回路。