MicroRNA‑21 promotes migration and invasion of glioma cells via activation of Sox2 and β‑catenin signaling.
MicroRNA‑21 promotes migration and invasion of glioma cells via activation of Sox2 and β‑catenin signaling.
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DOI：
10.3892/mmr.2016.5971
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发表时间：
2017-01
影响因子：
3.4
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Luo G;Luo W;Sun X;Lin J;Wang M;Zhang Y;Luo W;Zhang Y
据报道，microRNA 21 (miR-21) 的表达在多种类型的癌症中上调，包括恶性神经胶质瘤。然而，其在胶质瘤中的功能和机制仍有待充分阐明。本研究建立了miRNA-21过表达和敲低细胞系，使用SRY-box 2 (Sox2)小干扰RNA (siRNA)来敲低表达，并将Sox2 cDNA克隆到pcDNA 3.1哺乳动物表达载体中进行异位表达。 BIO 和 XAV-939 分别用于 β-连环蛋白信号传导激活和敲低。 Transwell小室用于测定细胞迁移的能力。本研究确定miR-21表达增加显着促进神经胶质瘤细胞的迁移和侵袭，同时伴有Sox2蛋白表达上调。 Sox2过表达还促进神经胶质瘤细胞迁移和侵袭，而Sox2 siRNA显着降低miR-21增强的神经胶质瘤细胞迁移和侵袭，表明Sox2可能是miR-21功能的关键介质。此外，miR-21还上调了β-连环蛋白的蛋白表达水平，而抗miR-21和Sox2敲低则显着降低了β-连环蛋白的表达。 BIO 是一种 β-连环蛋白特异性激动剂，可增强神经胶质瘤细胞的迁移和侵袭。 XAV-939是β-catenin信号传导的抑制剂，显着抑制胶质瘤细胞的迁移和侵袭，表明β-catenin可能与miR-21和Sox2诱导的胶质瘤细胞侵袭有关。值得注意的是，BIO 恢复了被 Sox2 siRNA 和抗 miR-21 抑制的神经胶质瘤细胞的迁移和侵袭潜力。这些发现表明 β-catenin 可能是 miR-21 和 Sox2 的重要下游介质。因此，本研究确定了miR-21/Sox2/β-catenin信号通路可能调控人胶质瘤细胞的迁移和侵袭。
The expression of microRNA 21 (miR-21) has been reported to be upregulated in various types of cancer, including malignant gliomas. However, its functions and mechanisms in glioma remain to be fully elucidated. The present study established miRNA-21 overexpression and knockdown cell lines using SRY-box 2 (Sox2) small interfering RNA (siRNA) to knockdown expression and Sox2 cDNA was cloned into pcDNA 3.1 mammalian expression vector for ectopic expression. BIO and XAV-939 were used for β-catenin signaling activation and knockdown, respectively. Transwell chambers were used to assay the capacity of cells to migrate. The present study determined that increased expression of miR-21 significantly promoted the migration and invasion of glioma cells, which was accompanied by an upregulated expression of the Sox2 protein. Sox2 overexpression also promoted glioma cell migration and invasion, whereas Sox2 siRNA markedly reduced the miR-21-enhanced migration and invasion of glioma cells, indicating Sox2 may act as a crucial mediator of miR-21 function. Furthermore, miR-21 also upregulated the protein expression level of β-catenin, whereas anti-miR-21 and Sox2 knockdown significantly reduced β-catenin expression. BIO, a β-catenin specific agonist, enhanced migration and invasion of glioma cells. XAV-939, an inhibitor of β-catenin signaling, markedly inhibited the migration and invasion of glioma cells, suggesting that β-catenin may be associated with miR-21- and Sox2-induced invasion of glioma cells. Notably, BIO restored the migration and invasion potential of glioma cells, which were inhibited by Sox2 siRNA and anti-miR-21. These findings indicated that β-catenin may be an important downstream mediator of miR-21 and Sox2. Therefore, the present study identified the miR-21/Sox2/β-catenin signaling pathway, which may regulate the migration and invasion of human glioma cells.