Identification of Differentially Expressed miRNAs and mRNAs in Vestibular Schwannoma by Integrated Analysis

Abstract

Background. Vestibular schwannoma (VS) is benign, slow-growing brain tumor that negatively impacts patient quality of life, which may cause even death. This study aimed to explore key genes and microRNAs (miRNAs) associated with VS. Methods. The mRNA and miRNA expression profiles of VS downloaded from Gene Expression Omnibus (GEO) database were included in this study to perform an integrated analysis. The differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) were identified. Then, functional annotation and protein-protein interaction networks (PPI) of DEmRNAs were constructed. DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. Results. A total of 2627 DEmRNAs (1194 upregulated and 1433 downregulated DEmRNAs) and 21 DEmiRNAs (12 upregulated and 9 downregulated DEmiRNAs) were identified. ISG15, TLE1, and XPC were three hub proteins of VS-specific PPI network. A total of 2970 DEmiRNAs-DEmRNAs pairs were obtained. Among which, hsa-miR-181a-5p, hsa-miR-106-5p, and hsa-miR-34a-5p were the top three DEmiRNAs that covered most DEmRNAs. The functional annotation of DEmiRNA-target DEmRNAs revealed that the DEmiRNA-target DEmRNAs were significantly enriched in cGMP-PKG signaling pathway, adrenergic signaling in cardiomyocytes, and pathways in cancer. Conclusion. The results of this present study may provide a comprehensive understanding for the roles of DEmRNAs and DEmiRNAs in the pathogenesis of VS and developing potential biomarkers of VS.

Transcriptional regulation of miR-30a by YAP impacts PTPN13 and KLF9 levels and Schwann cell proliferation

“…We focused on the relationship between YAP and miR-30a in Schwann cells due to the fact that miR-30a was found to be upregulated in human schwannomas, suggesting miR-30a overexpression could play a role in the development of these tumors. 18,19 Our findings demonstrate binding of YAP to the promoter of miR-30a and confirmed the expression of miR-30a to be induced by YAP expression. Although we did not directly assess the transcription factors through which YAP might serve to regulate miR-30a, we conducted a bioinformatic analysis of the genomic region surrounding the YAP-enriched peaks in the vicinity of the miR30a gene using GeneHancer.…”

“…In our study, we focused on the direct regulation of miR-30a expression by YAP, which has been shown to be upregulated in schwannomas. 18,19 Our efforts demonstrate YAP is a direct transcriptional activator of miR-30a and identify two common targets of YAP and miR-30a, PTPN13 and KLF9. Moreover, we find that the effects of YAP on Schwann cell proliferation are partially mediated through miR-30a regulation of PTPN13.…”

“…Moreover, the limited number of studies published to date has demonstrated YAP may carry out opposing roles in miRNA processing. In our study, we focused on the direct regulation of miR-30a expression by YAP, which has been shown to be upregulated in schwannomas ( 18 , 19 ). Our efforts demonstrate YAP is a direct transcriptional activator of miR-30a and identify two common targets of YAP and miR-30a, protein tyrosine phosphatase non-receptor type 1 ( PTPN13 ) and Kruppel like factor 9 ( KLF9 ) .…”

The role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors

“…Alternatively, transcriptional co-pressor (TLE1) is also one of the central nerves of the PPI network. PRICKLE1 mRNA is significantly down-regulated in vestibular schwannomas, while GALR1 is abundant in neuroactive ligand-receptor interactions, and both PRICKLE1 and GALR1 are targets of hsa-miR-30c-5p and hsa-miR-30a-5p, suggesting that hsa-miR-30 may play a key role in vestibular schwannomas [ 85 ]. In sporadic vestibular schwannomas, Erbb2-interacting protein (Erbin) gene was found to be up-regulated, while Erbin was able to participate in tumor production through neuregulin 1 (Nrg1) activation of pathways such as PI3K/AKT.…”

Integrated analysis and knockdown of RAB23 indicate the role of RAB23 in gastric adenocarcinoma

“…To further investigate the correlation between DEmiRNAs and DEmRNAs, we obtained DEmiRNA-DEmRNA interaction pairs (including downregulated DEmiRNAupregulated DEmRNA pairs and upregulated DEmiRNAdownregulated DEmRNA pairs) in tumor tissues vs. normal tissues. Detection of the target gene was performed as previously described (13).…”