Department of Magnetic Resonance Imaging, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China.
Department of Ultrasonics, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11894. Epub 2021 Feb 4.
Dysregulated circular RNAs (circRNAs) are involved in the carcinogenesis and progression of multiple human malignancies. Knowledge of circRNAs in glioma (GM) is limited and further study to uncover new therapeutic targets for GM is urgently required. The present study demonstrated that circ‑TOP2A was elevated in GM tissue specimens and cells and that circ‑TOP2A levels indicated an unfavorable clinical prognosis in GM. Functionally, circ‑TOP2A knockdown reduced viability, migration and invasion and triggered apoptosis in LN229 cells. Ectopic expression of circ‑TOP2A aggravated these malignant behaviors in U87MG cells. In terms of mechanism, RNA‑seq was performed to discover the potential targets regulated by circ‑TOP2A. Circ‑TOP2A acted as a competing endogenous RNA to upregulate sushi domain‑containing 2 (SUSD2) expression by sponging microRNA (miR) 346. Rescue assays revealed that the oncogenic function of circ‑TOP2A was partially dependent on its regulation of the miR‑346/SUSD2 axis. In conclusion, the present study identified that circ‑TOP2A promoted GM proliferation and aggressiveness via miR‑346/SUSD2 signaling, which is a potential prognostic biomarker and therapeutic target for GM.
失调的环状 RNA（circRNAs）参与多种人类恶性肿瘤的发生和发展。关于胶质瘤（GM）中 circRNAs 的知识有限，迫切需要进一步的研究来揭示 GM 的新治疗靶点。本研究表明，circ-TOP2A 在 GM 组织标本和细胞中升高，circ-TOP2A 水平表明 GM 的临床预后不良。功能上，circ-TOP2A 的敲低降低了 LN229 细胞的活力、迁移和侵袭，并触发了细胞凋亡。circ-TOP2A 的异位表达加剧了 U87MG 细胞中的这些恶性行为。就机制而言，进行了 RNA-seq 以发现受 circ-TOP2A 调节的潜在靶标。circ-TOP2A 通过海绵 microRNA（miR）346 作为竞争性内源性 RNA 上调含 sushi 结构域的 2 （SUSD2）的表达。挽救实验表明，circ-TOP2A 的致癌功能部分依赖于其对 miR-346/SUSD2 轴的调节。总之，本研究表明，circ-TOP2A 通过 miR-346/SUSD2 信号促进 GM 的增殖和侵袭，这是 GM 的一个潜在的预后生物标志物和治疗靶点。
