With more and more research on lncRNA and miRNA in various cancer fields, it has been found that lncRNA can be used as miRNA sponge to regulate mRNA, and more and more attention has been paid to ceRNA. Kai Ma et al. Constructed the ceRNA network (23) of pulmonary artistic hypertension. It is becoming more and more clear that many complex diseases, especially cancer, seldom can be attributed to one or several genomic variations alone (24). The study of ceRNA network is helpful to systematically understand the relevant processes of tumor occurrence, development, metastasis, prognosis, etc. In this study, large queues from TCGA database were used to identify the DElncRNAs, DEmRNAs and DEmiRNAs between LGG and normal tissues, so as to construct a prognosis related ceRNA network.
Through the Go analysis of DElncRNAs, DEmRNAs and DEmiRNAs, it was found that the differentially expressed genes in BP mostly led to the development of neurons, the formation of synapses and the release of synaptic signals. In CC, most of the differentially expressed genes constitute synaptic structure, while in MF, most of them are enriched in ion channel activity. These results show that the formation of LGG is inseparable from the formation of neuron structure, which seems to be closely linked to the development of epilepsy, and these conclusions need further experimental verification. Several key genes related to Go analysis are shown in Go circle plot map, among which several members of GABAR family appear in the results, which further verify the previous point of view. In KEGG analysis, cAMP signaling pathway is the most significant expression, which regulates many biological processes, such as cell migration, differentiation, proliferation and apoptosis (25). This seems to play an important role in the development of LGG. The axon guidance, glutamatergic synapse and GABAergic synapse signaling pathway indicate the cause of LGG epilepsy. Yinian Zhang et al found that glutamatergic synapse pathway is an important signal pathway related to epilepsy (26). We show the above important signal pathways, which will be helpful in the future development of LGG and epilepsy research. KM analysis of mRNA, lncrna and miRNA is helpful for molecular typing and targeted therapy of LGG.
The results of prognostic analysis showed that dlg2, GRIN1, HTR2A, kcnj3, KCNJ9, kif3c, SOCS3 and linc00599 were verified respectively (27, 28, 29, 30). In the constructed ceRNA network, we found 10 central key nodes through cytohubba: hsa-miR-320d,hsa-miR-30a-5p,hsa-miR-320c,hsa-miR-30b-5p,hsa-miR-30d-5p,hsa-miR-30e-5p,hsa-miR-320a,hsa-miR-137,has-miR-320b,has-miR-30c-5p.Hsa-mir-137 seems to be a key target in glioma cells, which has been reported in some studies.
Chen et al. found that miR-137down-regulated in glioma samples and glioma cells by qRT-PCR. They demonstrate that miR-137 deregulation is common in glioma, and restoration of its function inhibits cell proliferation and invasion, suggesting that miR-137 may act as a tumour suppressor (31). Deng et al. discovered miR-137 was significantly down regulated in astrocytoma tissues, and its expression level was inversely correlated with the clinical stage. They verified that miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1(32). Li et al. demonstrate that miR-137 expression is significantly downregulated in a cohort of 35 oligodendroglial tumors and nine glioma cell lines compared with normal brains. And miR-137 regulates growth of glioma cells and targets CSE1L(33). Sun et al. confirmed over expression of miR-137 in vitro by chemically synthesized miR-137 mimics suppressed the proliferation, inhibited cell cycle arrest in the G1/G0 phase, and induced cell apoptosis. Their findings indicate that miR-137 inhibits the growth of gliomas cells by directly targeting Rac1(34). In addition,Wang et al. presented the evidence that miR-30a-5p is overexpressed in glioma cell lines and glioma samples compared to the normal brain tissues, and its expression level is positively correlated with tumor grade of malignancy(35). In the core sub-network༌the high Cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) expression is a key role in glioma. CYP1B1 is involved in the xenobiotic detoxification metabolism and possibly activation of numerous procarcinogens and promutagens(36). Yu et al. demonstrate that extrasynaptic glutamate could in situ affect the arachidonic acid(AA) metabolism via brain CYP1B1, that can change the neuron-astrocyte reciprocal signaling(37). Besides༌Wnt/beta-catenin signaling regulates endothelial metabolic barrier function through Cyp1b1 transcription (38). There are few studies on relative lnrna, and it is only reported in the papillary gyroid carcinoma that Overexpression of long noncoding RNA SLC26A4-AS1 inhibits the epithelial-mesenchymal transition via the MAPK pathway (39).
At present, lack of research on ceRNA in LGG may be due to the limitations of in vitro experiments. In addition, this study has some limitations, which need to be further verified in vitro and in vivo. The results and conclusions of this study can be used as the basis for the establishment of mechanical hypothesis and for further experiments of clinical samples and cell lines. We hope that the systematic analysis of the interaction of ceRNA will help us to gain a better understanding of the molecular pathogenesis of LGG.