Meningioma, the most prevalent intracranial tumor, possesses a significant propensity for malignant transformation. Circular RNAs (circ-RNAs), a class of non-coding RNAs, have emerged as crucial players in tumorigenesis. This study explores the functional relevance of hsa_circ_0004872, a specific circ-RNA, in the context of meningioma. Molecular structure and stability of hsa_circ_0004872 were elucidated through PCR identification. Meningioma cell proliferation and apoptosis were assessed using the CCK-8 assay and flow cytometry, respectively. Gene and protein expression were analyzed via qRT-PCR and western blot. Molecular interactions were confirmed through dual-luciferase reporter gene and RIP assays. Hsa_circ_0004872, derived from exons 2 to 4 of the host gene MAPK1, demonstrated enhanced stability compared to its host MAPK1. Clinical data described that hsa_circ_0004872 was reduced in meningioma tissues and cell lines, and negatively correlated to poor survival rate of meningioma patients. Overexpression of hsa_circ_0004872 exhibited inhibitory effects on cell proliferation and promotion of apoptosis in vitro. Subsequent investigations unveiled a direct interaction between hsa_circ_0004872 and miR-190a-3p, leading to the activation of the PI3K/AKT signaling pathway through targeting PTEN. Notably, miR-190a-3p silence accelerated the apoptosis and proliferation inhibition of meningioma cells by inactivating PTEN/PI3K/AKT signaling, while miR-190a-3p overexpression showed an opposite effect, which greatly reversed the anti-tumor effects of hsa_circ_0004872 overexpression. In summary, our findings highlighted the intricate role of hsa_circ_0004872 in meningioma, shedding light on the regulatory mechanisms involving circ-RNAs in tumor progression. This positions hsa_circ_0004872 as a potential key regulatory factor in meningioma with implications for future therapeutic interventions. Hsa_circ_0004872 exhibits low expression in meningioma, correlating with a diminished survival rate among patients. Overexpression of hsa_circ_0004872 impedes meningioma cell proliferation while enhancing apoptosis. Hsa_circ_0004872 acts as a negative regulator of miR-190a-3p by functioning as a miRNA sponge. Upregulation of miR-190a-3p counteracts the anti-tumor effects induced by hsa_circ_0004872 overexpression in vitro. Inhibition of miR-190a-3p reduces cell proliferation and heightens apoptosis by targeting the PTEN/PI3K/AKT signaling pathway.

中文翻译：

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Hsa_circ_0004872 通过海绵 miR-190a-3p/PTEN 信号传导缓解脑膜瘤进展

脑膜瘤是最常见的颅内肿瘤，具有显着的恶变倾向。环状RNA（circ-RNA）是一类非编码RNA，已成为肿瘤发生的关键参与者。本研究探讨了 hsa_circ_0004872（一种特定的 circ-RNA）在脑膜瘤中的功能相关性。通过PCR鉴定阐明了hsa_circ_0004872的分子结构和稳定性。分别使用 CCK-8 测定和流式细胞术评估脑膜瘤细胞增殖和凋亡。通过 qRT-PCR 和蛋白质印迹分析基因和蛋白质表达。通过双荧光素酶报告基因和 RIP 测定证实了分子相互作用。Hsa_circ_0004872 源自宿主基因 MAPK1 的外显子 2 至 4，与宿主 MAPK1 相比，稳定性增强。临床数据显示，hsa_circ_0004872在脑膜瘤组织和细胞系中减少，与脑膜瘤患者较差的生存率呈负相关。hsa_circ_0004872的过表达在体外表现出对细胞增殖的抑制作用和促进细胞凋亡的作用。随后的研究揭示了 hsa_circ_0004872 和 miR-190a-3p 之间的直接相互作用，导致通过靶向 PTEN 激活 PI3K/AKT 信号通路。值得注意的是，miR-190a-3p沉默通过失活PTEN/PI3K/AKT信号加速脑膜瘤细胞的凋亡和增殖抑制，而miR-190a-3p过表达则表现出相反的效果，大大逆转了hsa_circ_0004872过表达的抗肿瘤作用。总之，我们的研究结果强调了 hsa_circ_0004872 在脑膜瘤中的复杂作用，揭示了 circ-RNA 在肿瘤进展中的调节机制。这使得 hsa_circ_0004872 成为脑膜瘤的潜在关键调节因素，对未来的治疗干预具有影响。Hsa_circ_0004872 在脑膜瘤中表现出低表达，与患者生存率降低相关。hsa_circ_0004872 的过度表达会阻碍脑膜瘤细胞增殖，同时增强细胞凋亡。Hsa_circ_0004872 通过充当 miRNA 海绵，充当 miR-190a-3p 的负调节因子。miR-190a-3p 的上调可抵消体外 hsa_circ_0004872 过表达诱导的抗肿瘤作用。抑制 miR-190a-3p 通过靶向 PTEN/PI3K/AKT 信号通路来减少细胞增殖并增加细胞凋亡。