Department of Pediatric Neurosurgery, ZhuJiang Hospital of Southern Medical University, Guangzhou 510282, China.
Department of Pediatric Neurosurgery, ZhuJiang Hospital of Southern Medical University, Guangzhou 510282, China.
J Clin Neurosci. 2021 Apr;86:87-96. doi: 10.1016/j.jocn.2021.01.020. Epub 2021 Feb 2.
Medulloblastoma (MB), the most common malignant childhood brain tumor, is a serious threat to life. Circular RNA (circRNA) is involved in the development of various cancers, including MB. We aimed to explore the role of circRNA spindle and kinetochore associated complex subunit 3 (circ-SKA3) in MB progression. Circ-SKA3 expression was elevated in MB tissues and cells. Depleted expression of circ-SKA3 inhibited MB cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest, and circ-SKA3 knockdown inhibited MB growth in vivo. Mechanism analyses revealed that circ-SKA3 directly targeted miR-326 that could bind to ID3, and circ-SKA3 decoyed miR-326 to increasing ID3 expression. Rescue experiments showed that miR-326 inhibition reversed the effects of circ-SKA3 knockdown, and ID3 overexpression recovered MB cell proliferation, migration and invasion blocked by miR-326 restoration. In conclusion, circ-SKA3 functioned as an oncogene to promote the development of MB by increasing ID3 expression via decoying miR-326, hinting that circ-SKA3 might be a therapeutic target of MB.
髓母细胞瘤（MB）是最常见的儿童脑恶性肿瘤，是对生命的严重威胁。环状 RNA（circRNA）参与多种癌症的发展，包括 MB。我们旨在探索环状 RNA 纺锤体和动粒相关复合物亚基 3（circ-SKA3）在 MB 进展中的作用。circ-SKA3 在 MB 组织和细胞中表达升高。circ-SKA3 表达下调抑制 MB 细胞增殖、迁移和侵袭，诱导细胞凋亡和细胞周期停滞，circ-SKA3 敲低抑制体内 MB 生长。机制分析表明，circ-SKA3 可直接靶向 miR-326，miR-326 可与 ID3 结合，circ-SKA3 诱饵 miR-326 可增加 ID3 的表达。挽救实验表明，miR-326 抑制逆转了 circ-SKA3 敲低的作用，而 ID3 的过表达恢复了 miR-326 恢复阻断的 MB 细胞增殖、迁移和侵袭。总之，circ-SKA3 通过诱饵 miR-326 增加 ID3 表达，发挥致癌基因的作用，促进 MB 的发展，提示 circ-SKA3 可能是 MB 的治疗靶点。
