Background/Aims: The present study was aimed at exploring the role of long noncoding RNA (lncRNA) FOXD2-AS1 in the development and progression of glioma and the underlying mechanism of FOXD2-AS1/miR-185-5p/HMGA2 network in glioma via regulation of PI3K/Akt signaling pathway.Methods: Microarray analysis was used for preliminary screening for candidate lncRNAs and mRNAs in glioma tissues. qRT-PCR and Western blot were used to determine the expression of FOXD2-AS1. The potential effects of FOXD2-AS1 on the viability, mobility and apoptosis of glioma cells were evaluated using MTT assay, Transwell assays and flow cytometry. The xenograft tumor model was performed to examine the influence of the lncRNA FOXD2-AS1/miR-185-5p/HMGA2 network on the biological functions of glioma cells. Luciferase assay and immunoprecipitation assay were examined to dissect molecular mechanisms.Results: LncRNA FOXD2-AS1 was overexpressed in human glioma, and upregulated FOXD2-AS11 expression indicated higher WHO grade (p < 0.05). MiR-185-5p was downregulated, whereas HMGA2 was upregulated in glioma tissues in comparison with para-carcinoma tissues. FOXD2-AS1 could regulate the expression of HMGA2 via miR-185-5p. Knockdown of FOXD2-AS1 significantly inhibited proliferation and metastatic potential of glioma cells, whereas endogenous expression FOXD2-AS1 inhibited the glioma cell activity through targeting HMGA2.Conclusions: lncRNA FOXD2-AS1 acted as a sponge of miR-185-5p and influenced the PI3K/Akt signaling pathway through regulating HMGA2. LncRNA FOXD2-AS1 modulated HMGA2 and PI3K/Akt downstream signaling through sponging miR-185-5p, thereby promoting tumorigenesis and progression of glioma.

Recent studies have found that the acetaldehyde dehydrogenase 1A3 (ALDH1A3) gene is a marker of glioma stem cells. A total of 115 brain glioma specimens were collected and classified into grade I–IV, while non‐tumor brain tissue specimens, taken from 12 patients of vascular malformation surgery, were used as control. ALDH1A3 gene promoter methylation in glioma tissues was detected by pyrosequencing, while immunohistochemistry and western blot were used to detect ALDH1A3 protein expressions in different grades of glioma tissues and normal brain tissues. The expression of ALDH1A3 in the glioma cell line U87 was detected by quantitative real‐time polymerase chain reaction and RNA‐Seq technology was applied to investigate differentially expressed genes before and after silencing the ALDH1A3 gene. Among the 115 glioma tissue specimens, 50 (43.48%) showed low and 65 (56.52%) high expression of ALDH1A3, but no expression was detected in the control. Univariate and multivariate COX regression analyses showed that the patient's tumor pathological grade, the methylation status of ALDH1A3 promoter, and the expression of ALDH1A3 protein were risk factors for progression‐free survival (PFS) and overall survival (OS) (all P < 0.05) and the OS of mice with silenced ALDH1A3 in a glioma nude mouse model was prolonged. U87 experiments revealed that ALDH1A3 expression had significant effects on apoptosis, proliferation, cell cycle, mitochondrial membrane potential, glucose consumption, lactate production, invasion ability, and expression of the pyruvate kinase M2 (PKM2) and hexokinase 2 (HK2) in glioma cells. ALDH1A3 protein expression is a marker for poor PFS and OS in glioma patients.

This article has been retracted: Aging has completed its investigation of this paper. We found multiple internal duplications and overlap between some of the transwell assay images used for Figures 3C,E and 5C,D,F and data published the preceding year by other authors [1]. The authors reply that "There are some irreproducible data (Figure 2 and 3) in our manuscript." An institutional investigation has concluded that the figures are unreliable and that much of the additional data in the paper cannot be reliably verified from records. Together, these issues decrease confidence in the integrity of the experimental findings reported. Consequently, all authors agreed that the article should be retracted. The authors sincerely apologize to the scientific community for any confusion and any unintended harm derived from the publication of this paper.