LncRNA FOXD1‐AS1 acts as a potential oncogenic biomarker in glioma

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.

Unveiling ncRNA regulatory axes in atherosclerosis progression

“…NATs is a highly heterogeneous group of lncRNAs, transcribed from the complementary chain of target genes in an antisense orientation, that regulate post‐transcriptionally gene expression via RNA:RNA interactions with mRNA or miRNAs [196]. In this sense, oncogenic lncRNA FOXD1‐AS1 (FOXD1‐antisense 1), the antisense transcript of the gene FOXD1, was reported to interact with miR339‐5p and miR342‐3p [197], tumor suppressor TP73‐AS1 sponged miR‐941 [198], while TSPAN31, the natural antisense transcript of cyclin dependent kinase 4 (CDK4), interacted with miR‐135b in hepatocellular carcinoma causing TSPAN31 silencing and the subsequent upregulation of CDK4 [199].…”

Long non‐coding RNA LEF1‐AS1 is involved in the progression of retinoblastoma through regulating the Wnt/β‐catenin pathway

“…21 Moreover, the high expression of LEF1-AS1 in glioblastoma tissue specimens was also confirmed through RT-qPCR. 21 Subsequently, LEF1-AS1 was generally found to be overexpressed in human cancers including lung cancer, 14,15 esophageal squamous cell carcinoma, 16 breast, 17 colorectal, 18,19 and prostate cancer, 20 and oral squamous cell carcinoma. 23 Congrains-Castillo et al 22 suggested that normal hematopoietic stem cells have significantly higher LEF1-AS1 expression than myeloid malignant cells.…”

“…[9][10][11][12] The lymphoid enhancer binding factor 1 antisense RNA 1 (LEF1-AS1) is a highly conserved transcript located in the human chromosome 4q25. 13 LEF1-AS1 has been suggested to play a role as a tumour-associated lncRNA in several types of human cancers, such as lung cancer, 14,15 esophageal squamous cell carcinoma, 16 breast, 17 colorectal, 18,19 and prostate cancers, 20 glioblastoma, 21 myeloid malignancy, 22 and oral squamous cell carcinoma. 23 Therefore, we hypothesized that LEF1-AS1 might also function as an oncogenic lncRNA in retinoblastoma.…”

Long Non-Coding RNA FOXD1-AS1 Promotes the Progression and Glycolysis of Nasopharyngeal Carcinoma by Sustaining FOXD1 Expression

“…Similarly, the overexpression of FOXD1-AS1 contributed to cell growth, migration, and metastasis, and inhibited the apoptosis of NPC cells. Additionally, Gao et al [17] reported that FOXD1-AS1 promotes cell proliferation and migration and decreases apoptosis by regulating eIF5a protein levels in gliomas.…”

“…Thus, further investigation into lncRNA regulatory mechanisms to provide prognostic biomarkers and therapeutic targets for NPC patients would be bene cial. FOXD1 antisense RNA1 (FOXD1-AS1) is a novel lncRNA that has been reported to function as a potential oncogenic biomarker in glioma [17]. Nevertheless, the pivotal role of FOXD1-AS1 in NPC remains to be elucidated.…”