Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiao Tong University, No. 277 Yanta Xi Road, Xi'an, 710061, Shaanxi Province, People's Republic of China.
Department of Neurosurgery, Yulin First Hospital Affiliated to Xi'an Jiao Tong University, Yulin, 719000, People's Republic of China.
Mol Med. 2020 Apr 8;26(1):29. doi: 10.1186/s10020-020-00159-1.
Glioma has the characteristics of high incidence and mortality, and is a common malignant tumor of the central nervous system. Circular RNAs (circRNAs) have been reported to play vital roles in progression of cancer including glioma, and circKIF4A is up-regulated in glioma tissues. However, its role and mechanisms in gliomas are unclear.
circKIF4A and miR-139-3p were determined by qRT-PCR. Transwell assay, wound-healing assay, cell colony formation and flow cytometry were performed to measure cell invasion, migration, proliferation and apoptosis. Western blotting was used to evaluate Wnt/β-catenin pathway-related protein. Luciferase reporter assays confirmed the relationship among circKIF4A, miR-139-3p and Wnt5a. Sphere formation was performed to measure the ability of glioma-initiating cells (GICs) spheroid formation. A nude mouse xenograft model was established and immunohistochemical staining was used to detect Ki-67 and Wnt5a levels.
circKIF4A and Wnt5a were up-regulated and miR-139-3p was down-regulated in both glioma cells and tissues. circKIF4A promoted Wnt5a expression by sponging miR-139-3p. Knockdown of circKIF4A inhibited the colony formation ability, migration and invasion, and promoted the apoptosis of glioma cells by regulating miR-139-3p. Knockdown of circKIF4A inhibited Wnt/β-catenin signaling pathway and proliferation-related signal via miR-139-3p. Furthermore, knockdown of circKIF4A or overexpression of miR-139 suppressed the ability of sphere formation of GICs and inhibitd Wnt/β-catenin signaling pathway and proliferation-related signal in GICs. Additionally, depletion of circKIF4A decreased the expression level of Wnt5a and Ki-67, inhibited tumorigenesis in xenograft modes.
circKIF4A was overexpressed in glioma, and knockdown of circKIF4A suppressed glioma progression via miR-139-3p/Wnt5a axis. The results indicated that circKIF4A may be a potential target for clinical treatment of glioma.
脑胶质瘤具有发病率和死亡率高的特点，是中枢神经系统常见的恶性肿瘤。环状 RNA（circRNA）已被报道在包括脑胶质瘤在内的癌症进展中发挥重要作用，circKIF4A 在脑胶质瘤组织中上调。然而，其在脑胶质瘤中的作用和机制尚不清楚。
通过 qRT-PCR 检测 circKIF4A 和 miR-139-3p。通过 Transwell assay、划痕愈合 assay、细胞集落形成和流式细胞术检测细胞侵袭、迁移、增殖和凋亡。Western blot 用于评估 Wnt/β-catenin 通路相关蛋白。荧光素酶报告实验证实 circKIF4A、miR-139-3p 和 Wnt5a 之间的关系。球体形成实验用于检测脑胶质瘤起始细胞（GICs）球体形成能力。建立裸鼠异种移植模型，免疫组织化学染色检测 Ki-67 和 Wnt5a 水平。
circKIF4A 和 Wnt5a 在脑胶质瘤细胞和组织中上调，miR-139-3p 下调。circKIF4A 通过海绵吸附 miR-139-3p 促进 Wnt5a 表达。敲低 circKIF4A 抑制脑胶质瘤细胞集落形成能力、迁移和侵袭，并通过调节 miR-139-3p 促进细胞凋亡。敲低 circKIF4A 通过 miR-139-3p 抑制 Wnt/β-catenin 信号通路和增殖相关信号。此外，敲低 circKIF4A 或过表达 miR-139-3p 抑制 GICs 的球体形成能力，并抑制 GICs 中的 Wnt/β-catenin 信号通路和增殖相关信号。此外，circKIF4A 的耗竭降低了 Wnt5a 和 Ki-67 的表达水平，抑制了异种移植模型中的肿瘤发生。
circKIF4A 在脑胶质瘤中高表达，敲低 circKIF4A 通过 miR-139-3p/Wnt5a 轴抑制脑胶质瘤进展。结果表明，circKIF4A 可能是脑胶质瘤临床治疗的潜在靶点。
