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LncRNA FOXD1-AS1 acts as a potential oncogenic biomarker in glioma.

ABSTRACT: AIMS:Altered 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. METHODS:Expression 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. RESULTS:FOXD1-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. CONCLUSIONS:These 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.

SUBMITTER: Gao YF

PROVIDER: S-EPMC6930828 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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LncRNA FOXD1-AS1 acts as a potential oncogenic biomarker in glioma.

Gao Yuan-Feng YF Liu Jun-Yan JY Mao Xiao-Yuan XY He Zheng-Wen ZW Zhu Tao T Wang Zhi-Bin ZB Li Xi X Yin Ji-Ye JY Zhang Wei W Zhou Hong-Hao HH Liu Zhao-Qian ZQ

CNS neuroscience & therapeutics 20190517 1

<h4>Aims</h4>Altered 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.<h4>Methods</h4>Expression profile chip and qPCR were used to screen and identify FOXD1-AS1. Glioma cells were transfected ...[more]

PMID: 31102349

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Project description:Background Glioma is characterized by high morbidity, high mortality, and poor prognosis. Despite tremendous advances in the treatment of glioma, the prognosis of patients with glioma is still unsatisfactory. There is an urgent need to discover novel molecular markers that effectively predict prognosis in patients with glioma. The investigation of the role of WEE2-AS1 in various tumors is an emerging research field, but the biological function and prognostic value of WEE2-AS1 in glioma have rarely been reported. This study aimed to assess the value of WEE2-AS1 as a potential prognostic marker of glioma. Methods Gene expression (RNA-Seq) data of patients with glioma were extracted from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. The Wilcoxon rank sum test was used to analyze the expression of WEE2-AS1 in the cells and tissues of glioma. The Kruskal–Wallis rank sum test, Wilcoxon rank sum test, and logistic regression were used to evaluate the relationship between clinical variables and expression of WEE2-AS1. Cox regression analysis and the Kaplan–Meier method were used to evaluate the prognostic factors in glioma. A nomogram based on Cox multivariate analysis was used to predict the impact of WEE2-AS1 on glioma prognosis. Gene Set Enrichment Analysis (GSEA) was used to identify key WEE2-AS1-associated signaling pathways. Spearman’s rank correlation was used to elucidate the association between WEE2-AS1 expression and immune cell infiltration levels. Results We found that WEE2-AS1 was overexpressed in a variety of cancers, including glioma. High expression of WEE2-AS1 was associated with glioma progression. We determined that the expression of WEE2-AS1 might be an independent risk factor for the survival and prognosis of patients with glioma. We further observed that the mechanism of WEE2-AS1-mediated tumorigenesis involved neuroactive ligand-receptor interaction, cell cycle, and the infiltration of immune cells into the glioma microenvironment. Conclusion These findings demonstrate that WEE2-AS1 is a promising biomarker for the diagnosis and prognosis of patients with glioma. An increased understanding of its effects on the regulation of cell growth may lead to the development of clinical applications that improve the prognostic status of patients with glioma. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-023-10594-y.

Dataset Information

LncRNA FOXD1-AS1 acts as a potential oncogenic biomarker in glioma.

Publications

LncRNA FOXD1-AS1 acts as a potential oncogenic biomarker in glioma.

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