LncRNA NFIA-AS2 promotes glioma progression through modulating the miR-655-3p/ZFX axis

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RESEARCH ARTICLE

LncRNA NFIA‑AS2 promotes glioma progression through modulating the miR‑655‑3p/ZFX axis Jun Xin1 · Yu‑Hong Zhao1 · Xi‑Yun Zhang1 · Li‑Qiang Tian2 Received: 5 June 2020 / Accepted: 2 August 2020 © Japan Human Cell Society 2020

Abstract 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 miR655-3p 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. Keywords  Long non-coding RNA · NFIA-AS2 · Glioma · miR-655-3p · ZFX

Introduction Glioma is the most common and lethal malignant disease in the nervous system neoplasm, which include the low-grade glioma (I–II) and high-grade glioma (III–IV) [1, 2]. Among them, glioblastoma multiforme (GBM) as high-grade glioma is the most aggressive type and accounts for over 65% of all malignant brain tumors [2]. Although surgery, radiation, chemotherapy and target therapy have significantly improved the therapy and provided the tremendous clinical benefits for glioma patients, the overall prognosis remains extremely poor [3]. The 5-year survival rate remains dismal due to the aggressive behavior and unacceptable high rate of tumor recurrence [2, 3]. Therefore, it is very necessary to explore * Li‑Qiang Tian [email protected] 1



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

2

the novel biomarkers and elucidate the molecular mechanisms of glioma progression for the diagnosis and therapy of glioma patients. Long non-coding RNAs (lncRNAs) belong to non-coding RNAs, which constitute no more than 200 nucleotides and lack protein coding function [4]. Increasing studies have indicated that lncRNAs play oncogenic or suppressive roles in the tumorigenesis and progression of various cancers including glioma [5, 6]. It has