Abstract
AimsAltered activities of long noncoding RNAs (lncRNAs) have been associated with cancer development, and lncRNA FOXD1‐AS1 (FOXD1‐AS1) is the antisense transcript of the gene encoding for FOXD1, known for its role as an oncogene in several tumor types including glioma. However, the role of FOXD1‐AS1 in the differentiation and progression of glioma is not well known.MethodsExpression profile chip and qPCR were used to screen and identify FOXD1‐AS1. Glioma cells were transfected with siRNA or eukaryotic expression vector to observe FOXD1‐AS1 function in vitro and in vivo. Dual luciferase reporter gene analysis, Western blot, and ChIRP‐MS were used to detect microRNAs and protein that combine with FOXD1‐AS1.ResultsFOXD1‐AS1 was upregulated and directly correlated with the glioma grade, and it was localized in both the nucleus and the cytoplasm of the glioma cell. FOXD1‐AS1 silencing caused tumor suppressive effects via inhibiting cell proliferation, migration, and apoptosis, while FOXD1‐AS1 overexpression resulted in opposite effects. Additionally, in vivo experiments showed that FOXD1‐AS1 knockdown reduced tumor volume and weight. More importantly, mechanical studies revealed that FOXD1‐AS1 targeted both miR339‐5p and miR342‐3p (miR339/342). Furthermore, protein eukaryotic translation initiation factor 5 subunit A (eIF5a) resulted a direct target of FOXD1‐AS1.ConclusionsThese data indicated that FOXD1‐AS1, a miR339/342 target, affected biological processes via protein eIF5a; thus, it might be considered as a new therapeutic target for glioblastoma.
Highlights
Glioma is a common malignant tumor affecting the brain and/or the spine, accounting for approximately 40% of the intracranial tu‐ mors.[1,2] The WHO classifies gliomas into four levels, where grade I is a benign glioma, II is a low‐grade glioma, and III‐IV are highly malignant gliomas
With the rapid development of epigenetics in recent years, plenty of long noncoding RNAs (lncRNAs) that are aberrantly expressed in glioma can affect cancer progression
The cur‐ rent study found that Forkhead Box D1 (FOXD1)‐AS1 was upregulated and directly correlated with the glioma grade
Summary
Glioma is a common malignant tumor affecting the brain and/or the spine, accounting for approximately 40% of the intracranial tu‐ mors.[1,2] The WHO classifies gliomas into four levels, where grade I is a benign glioma, II is a low‐grade glioma, and III‐IV are highly malignant gliomas. Researchers found that lncRNAs play a critical regula‐ tory role in dosage compensation effect, epigenetic regulation, cell cycle regulation, cell differentiation regulation, and many other life activities.[11,12]. Unlike their shorter counterparts, such as microRNAs (miRNAs) and other smaller noncoding RNAs, lncRNAs can regulate downstream target genes by cis‐ and trans‐regulatory effects.[13,14]. We detected the expression, functional role, and underlying mechanism of FOXD1‐AS1 in glioma. Our findings reveal that FOXD1‐AS1, a miR339/342 target, affected biologi‐ cal processes via protein eIF5a; it might be considered as a novel emerging oncogenic biomarker and a potential target against glioma
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