BACKGROUND Astroglioma is the most common primary tumor of the central nervous system. Currently, there is no effective treatment for astroglioma. In the present study, the extract (L3) from Ganoderma Lucidum (G. lucidum) was found to inhibit the growth of astroglioma U87 cells and change the expression of circular RNAs (circRNAs). One of these, including the circular NF1-419 (circNF1-419), was of interest because NF1 gene is a classic tumor suppressor gene. OBJECTIVES The functional role of circ-NF1-419 in the inhibition of astroglioma cells remains unknown. This study focuses on the role of circNF1-419 in functional abnormalities of U87 astroglioma cells and aims to elaborate on its regulatory mechanism. METHODS The circNF1-419 overexpressing U87 (U87-NF1-419) cells were constructed. We generated U87-NF1-419 to evaluate the role of circNF1-419 on cell cycle, apoptosis, proliferation, tumor growth and metabolic regulation. Finally, we used docking screening to identify compounds in G. lucidum extracts that target circ-419. RESULTS U87-NF1-419 can promote cell apoptosis and regulate lipid metabolism through glycerophospholipid metabolism and retrograde endocannabinoid signaling. Further examinations revealed that the expression of metabolic regulators, such as L-type voltage-operated calcium channels (L-VOCC), phospholipase C-β3 (PLCβ3), Mucin1, cationic amino acid transporter 4 (CAT4), cationic amino acid transporter 1 (CAT1) and a kinase (PRKA) anchor protein 4 (AKAP4) was inhibited, while phosphatidylserine synthase 1 (PTDSS1) was enhanced in U87-NF1-419 cells. In vivo experiments showed that circNF1-419 inhibits tumor growth in BALB/C nude mice, and enhanced AKAP4 and PTDSS1 in tumor tissues. The virtual docking screening results supported that ganosporeric acid A, ganodermatriol, ganoderic acid B and α-D-Arabinofuranosyladenine in L3 could activate circNF1-419 in astroglioma treatment. CONCLUSION This study indicated that circNF1-419 could be a therapeutic target for the clinical treatment of astroglioma. L3 from Ganoderma Lucidum (G. lucidum) could inhibit astroglioma growth by activating circNF1-419.

中文翻译：

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环状 RNA NF1-419 通过调节星形胶质瘤细胞的脂质代谢抑制增殖并诱导细胞凋亡。

背景星形胶质瘤是中枢神经系统最常见的原发性肿瘤。目前，星形胶质瘤尚无有效的治疗方法。在本研究中，发现灵芝 (G. lucidum) 的提取物 (L3) 可抑制星形胶质瘤 U87 细胞的生长并改变环状 RNA (circRNA) 的表达。其中之一，包括环状 NF1-419 (circNF1-419)，是令人感兴趣的，因为 NF1 基因是经典的肿瘤抑制基因。目的 circ-NF1-419 在抑制星形胶质瘤细胞中的功能作用仍然未知。本研究重点关注circNF1-419在U87星形胶质瘤细胞功能异常中的作用，旨在阐述其调控机制。方法构建circNF1-419过表达U87（U87-NF1-419）细胞。我们生成了 U87-NF1-419 来评估 circNF1-419 在细胞周期、细胞凋亡、增殖、肿瘤生长和代谢调节中的作用。最后，我们使用对接筛选来鉴定灵芝提取物中靶向 circ-419 的化合物。结果 U87-NF1-419可通过甘油磷脂代谢和逆行内源性大麻素信号传导促进细胞凋亡并调节脂质代谢。进一步检查发现代谢调节因子的表达，如 L 型电压操作钙通道 (L-VOCC)、磷脂酶 C-β3 (PLCβ3)、Mucin1、阳离子氨基酸转运蛋白 4 (CAT4)、阳离子氨基酸转运蛋白 1 (CAT1) 和激酶 (PRKA) 锚蛋白 4 (AKAP4) 被抑制，而磷脂酰丝氨酸合酶 1 (PTDSS1) 在 U87-NF1-419 细胞中得到增强。体内实验表明，circNF1-419 可抑制 BALB/C 裸鼠的肿瘤生长，并增强肿瘤组织中的 AKAP4 和 PTDSS1。虚拟对接筛选结果支持L3中的灵芝酸A、灵芝三醇、灵芝酸B和α-D-Arabinofuranosyladenine在星形胶质瘤治疗中可以激活circNF1-419。结论 本研究表明circNF1-419可作为星形胶质瘤临床治疗的治疗靶点。来自灵芝 (G. lucidum) 的 L3 可以通过激活 circNF1-419 来抑制星形胶质瘤的生长。结论 本研究表明circNF1-419可作为星形胶质瘤临床治疗的治疗靶点。来自灵芝 (G. lucidum) 的 L3 可以通过激活 circNF1-419 来抑制星形胶质瘤的生长。结论 本研究表明circNF1-419可作为星形胶质瘤临床治疗的治疗靶点。来自灵芝 (G. lucidum) 的 L3 可以通过激活 circNF1-419 来抑制星形胶质瘤的生长。