环状 RNA Circ-ITCH 通过靶向 miR-106a-5p/SASH1 轴抑制神经胶质瘤细胞的增殖和侵袭。
CircRNA Circ-ITCH Inhibits the Proliferation and Invasion of Glioma Cells Through Targeting the miR-106a-5p/SASH1 Axis.
机构信息
Department of Neurosurgery, Nanjing First Hospital, Nanjing, China.
* Both the authors contributed equally to this article.
出版信息
Cell Transplant. 2021 Jan-Dec;30:963689720983785. doi: 10.1177/0963689720983785.
Circ-ITCH, a novel circRNA, was generated from several exons of itchy E3 ubiquitin protein ligase (ITCH). Recently, circ-ITCH has been demonstrated to be involved in cancer development. However, there have been few investigations on the specific role of circ-ITCH in glioma. In this study, we performed quantitative real-time polymerase chain reaction analysis and identified that circ-ITCH was significantly downregulated in glioma tissues and cell lines. The function assays showed that upregulation of circ-ITCH inhibited glioma cell proliferation and invasion as well as reduced cell growth . Moreover, miR-106a-5p was found serving as a target of circ-ITCH and miR-106a-5p mimics could reverse the inhibitory effect of circ-ITCH on glioma cell proliferation and invasion. We also revealed that circ-ITCH increased SASH1 expression by sponging miR-106a-5p in glioma cells. In addition, SASH1 downregulation could abrogate the suppressive effect of circ-ITCH on glioma progression. Taken together, our results suggested that circ-ITCH could suppress glioma cell proliferation and invasion via regulating the miR-106a-5p/SASH1 axis, elucidating a novel molecular target for glioma treatment.
环状 RNA（circRNA）是一类新型的内源性非编码 RNA，广泛存在于真核生物中。circRNA 通常由前体 mRNA 反向剪接形成，具有高度稳定性和组织特异性。与线性 RNA 相比，circRNA 不易被 RNA 外切酶降解，因此在细胞内的半衰期更长。此外，circRNA 还可以通过与 RNA 结合蛋白（RBPs）相互作用，调节基因表达和细胞功能。近年来，circRNA 在肿瘤发生、发展和转移等过程中的作用受到了广泛关注。
circITCH 是由瘙痒 E3 泛素蛋白连接酶（ITCH）的几个外显子产生的新型 circRNA。最近，circ-ITCH 已被证明参与癌症的发展。然而，关于 circ-ITCH 在神经胶质瘤中的具体作用的研究甚少。在本研究中，我们进行了定量实时聚合酶链反应分析，发现 circ-ITCH 在神经胶质瘤组织和细胞系中显著下调。功能测定表明，circ-ITCH 的上调抑制了神经胶质瘤细胞的增殖和侵袭，并降低了细胞生长。此外，发现 miR-106a-5p 是 circ-ITCH 的靶标，miR-106a-5p 模拟物可以逆转 circ-ITCH 对神经胶质瘤细胞增殖和侵袭的抑制作用。我们还揭示了 circ-ITCH 通过海绵吸附 miR-106a-5p 增加神经胶质瘤细胞中的 SASH1 表达。此外，SASH1 下调可以消除 circ-ITCH 对神经胶质瘤进展的抑制作用。总之，我们的研究结果表明，circ-ITCH 通过调节 miR-106a-5p/SASH1 轴抑制神经胶质瘤细胞的增殖和侵袭，为神经胶质瘤的治疗提供了新的分子靶点。
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