Department of Neurosurgery, Linyi Central Hospital, Linyi, 276400, Shandong, China.
Department of Neurosurgery, Linyi People's Hospital, No. 27 Jiefang Road, Lanshan District, Linyi, 276003, Shandong, China.
Hum Cell. 2020 Oct;33(4):1273-1280. doi: 10.1007/s13577-020-00408-9. Epub 2020 Aug 10.
Long non-coding RNAs (lncRNAs) are closely associated with tumorigenesis of various malignancies, including glioma. However, the roles of most lncRNAs in glioma remain undiscovered. The present study for the first time explored the roles of NFIA-AS2 in glioma. Based on informatic analyses by online database, lncRNA NFIA-AS2 in glioma tissues was overexpressed and further confirmed in glioma tissues and cells by quantitative real-time PCR (qRT-PCR). High expression of NFIA-AS2 was closely correlated with poor prognosis and might be an independent prognostic factor for PFS and OS. Functionally, silenced NFIA-AS2 could remarkably hinder glioma cell proliferation, migration and invasion, and cause the apoptosis. Mechanistic investigation disclosed that NFIA-AS2 interacted with miR-655-3p and inversely connected with miR-655-3p in glioma. Additionally, miR-655-3p was proved to regulate the expression of ZFX. Final rescue assay demonstrated that ZFX overexpression or miR-655-3p downregulation could neutralize the suppressive effects of NFIA-AS2 knockdown on glioma progression. In conclusion, this study firstly reported that NFIA-AS2 could promote the progression of glioma by targeting the miR-665-3p/ZFX axis, which highlighted that NFIA-AS2 could be a novel biomarker and therapeutic target for glioma patients.
长链非编码 RNA(lncRNAs)与各种恶性肿瘤的发生密切相关,包括神经胶质瘤。然而,大多数 lncRNA 在神经胶质瘤中的作用仍未被发现。本研究首次探讨了 NFIA-AS2 在神经胶质瘤中的作用。通过在线数据库的信息分析,发现神经胶质瘤组织中 lncRNA NFIA-AS2 过表达,并通过定量实时 PCR(qRT-PCR)进一步在神经胶质瘤组织和细胞中得到证实。NFIA-AS2 的高表达与预后不良密切相关,可能是 PFS 和 OS 的独立预后因素。功能上,沉默 NFIA-AS2 可显著抑制神经胶质瘤细胞的增殖、迁移和侵袭,并诱导细胞凋亡。机制研究表明,NFIA-AS2 与 miR-655-3p 相互作用,并与神经胶质瘤中的 miR-655-3p 呈负相关。此外,miR-655-3p 被证明可以调节 ZFX 的表达。最终的挽救实验表明,ZFX 的过表达或 miR-655-3p 的下调可以中和 NFIA-AS2 敲低对神经胶质瘤进展的抑制作用。总之,本研究首次报道 NFIA-AS2 可以通过靶向 miR-665-3p/ZFX 轴促进神经胶质瘤的进展,这表明 NFIA-AS2 可以作为神经胶质瘤患者的新型生物标志物和治疗靶点。