Differential Expression Profile of lncRNA in Glioma Cells and the Effect of lncRNA NKX3-1 on Glioma Cells Through Fem1b/SPDEF Pathway

Abstract

ObjectiveTo investigate the differential expression of lncRNA in glioma cells, as well as the effect of lncRNA NKX3-1 on glioma cells.MethodsGlioma-related data were first downloaded from the TCGA database and analyzed using bioinformatics, after which the lncRNA NKX3-1 was chosen for further experiments. The expression of the lncRNA NKX3-1 in glioma tumor samples was detected using qRT-PCR. The subcellular localization of lncRNA NKX3-1 was determined using fluorescence in situ hybridization (FISH). CCK-8, flow cytometry, cell scratch, and transwell assays were used to detect cell proliferation, apoptosis, and invasion. The downstream pathway of lncRNA NKX3-1 was investigated using luciferase assays and detected using western blot, transwell, and cell scratch assays.ResultsThe differential expression profile of lncRNA in glioma was obtained. NKX3-1 lncRNA was found to be significantly increased in glioma tumor tissues. LncRNA NKX3-1 was found in the nucleus. Proliferation, invasion, and migration of glioma cells were significantly increased (P <0.05) in the lncRNA NKX3-1 overexpression group, while apoptosis ability was significantly decreased (P <0.05). Tumor volume and weight were significantly increased in the lncRNA NKX3-1 overexpression group in nude mice (P <0.05). LncRNA NKX3-1 significantly increased the luciferase activity of Fem1b 3’-UTR-WT reporter genes (P <0.05) as well as the levels of SPDEF protein (P <0.05). The protein level of FEM1B was significantly reduced. Cell invasion and migration were significantly increased (P <0.05) in the lncRNA NKX3-1 overexpression group plus SPDEF group.ConclusionWe investigated the differential expression profile of lncRNAs in glioma and discovered that the lncRNA NKX3-1 plays an important role in cancer promotion via the Fem1b/SPDEF pathway.

Cracking the Code of Neuronal Cell Fate

“…We observed an increased expression of Spdef throughout the time-course of CGNs apoptosis and its down-regulation following NFs treatment ( Figure 1 and Figure 3 ) [ 43 ]. This evidence supports previous studies proposing its role as a tumor suppressor in various types of cancers [ 186 , 187 ]. In addition, altered expression of SPDEF has been found in Alzheimer’s disease patients and animal models, while a recent association was found between blood-based Spdef methylation and stress response, altered dopaminergic neurotransmission and increased vulnerability to substance abuse, suggesting its role as a biomarker for these pathological conditions [ 188 , 189 , 190 , 191 ].…”

lncRNA PDCD4-AS1 Promotes the Progression of Glioma by Regulating miR-30b-3p/METTL7B Signaling

“…Glioma is one of the most frequent tumor types in the human central nervous system; however, its treatment typically returns poor outcomes. Increasingly, research has made great achievements in developing target therapies for glioma [12,13,18,19]. In the past few decades, evidence has revealed that lncRNAs and miRNAs are key regulators of tumor proliferation and progression.…”

The role of SPDEF in cancer: promoter or suppressor

“…Some other scientists also hold the opinion that ATOH1 silencing causes SPDEF loss in human colon cancer [49]. lncRNA NKX3-1, as a kind of lncRNA, can promote SPDEF expression by targeting FEM1B, thus promoting the proliferation, invasion, and migration of glioma cells and inhibiting apoptosis [50]. miR-204 can regulates endogenous SPDEF mRNA at the post-transcriptional level to regulate SPDEF protein level [51].…”