Wu Quansheng, Yin Xiaofeng, Zhao Wenbo, Xu Wenli, Chen Laizhao
Department of neurosurgery, The Second Hospital of Shanxi Medical University, 030001, Taiyuan City, Shanxi Province, China.
Cell Death Discov. 2022 Apr 26;8(1):229. doi: 10.1038/s41420-022-00979-6.
Glioma is an intracranial malignant tumor and remains largely incurable. Circular RNAs are prominent modulators in glioma progression. This study investigated the function of circular RNA DLC1 (circDLC1) in the malignant proliferation of glioma cells. circDLC1 expression in glioma tissues and cells was determined using RT-qPCR. The effect of circDLC1 on the malignant proliferation of glioma cells was analyzed using CCK-8, colony formation, and EdU staining assays. METTL3, miR-671-5p, and CTNNBIP1 expressions were determined. N methyladenosine (mA) level of circDLC1 was analyzed using MeRIP. The binding relationship between miR-671-5p and circDLC1 or CTNNBIP1 was verified using RNA pull-down and dual-luciferase assays. A xenograft tumor model was established in nude mice to verify the effect of METTL3-mediated circDLC1 on glioma in vivo. circDLC1 was poorly expressed in glioma. circDLC1 overexpression suppressed glioma cell proliferation. Mechanically, METTL3-mediated mA modification enhanced circDLC1 stability and upregulated circDLC1 expression in glioma. circDLC1 upregulated CTNNBIP1 transcription by competitively binding to miR-671-5p. METTL3 overexpression repressed the malignant proliferation of glioma via circDLC1/miR-671-5p/CTNNBIP1 in vivo. Collectively, METTL3-mediated mA modification upregulated circDLC1 expression, and circDLC1 promoted CTNNBIP1 transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma.
胶质瘤是一种颅内恶性肿瘤，目前在很大程度上仍无法治愈。环状RNA是胶质瘤进展中的重要调节因子。本研究探讨了环状RNA DLC1（circDLC1）在胶质瘤细胞恶性增殖中的作用。采用RT-qPCR检测胶质瘤组织和细胞中circDLC1的表达。采用CCK-8、集落形成和EdU染色试验分析circDLC1对胶质瘤细胞恶性增殖的影响。检测METTL3、miR-671-5p和CTNNBIP1的表达。采用MeRIP分析circDLC1的N甲基腺苷（mA）水平。采用RNA下拉和双荧光素酶试验验证miR-671-5p与circDLC1或CTNNBIP1之间的结合关系。在裸鼠中建立异种移植肿瘤模型，以验证METTL3介导的circDLC1对体内胶质瘤的影响。circDLC1在胶质瘤中低表达。circDLC1过表达抑制胶质瘤细胞增殖。机制上，METTL3介导的mA修饰增强了circDLC1的稳定性，并上调了胶质瘤中circDLC1的表达。circDLC1通过竞争性结合miR-671-5p上调CTNNBIP1转录。METTL3过表达在体内通过circDLC1/miR-671-5p/CTNNBIP1抑制胶质瘤的恶性增殖。总的来说，METTL3介导的mA修饰上调了circDLC1的表达，circDLC1通过海绵化miR-671-5p促进CTNNBIP1转录，从而抑制胶质瘤的恶性增殖。
