Search

Background: Circular RNA (circRNA) has been demonstrated to play key roles in regulating glioma progression. Understanding the regulatory mechanism of circRNA in glioma is vital to reveal the pathogenesis of glioma and develop novel therapeutic strategies. Therefore, our study focuses on the role and underlying mechanism of Circ_CLIP2 in glioma., Methods: The expression of Circ_CLIP2, miR-195-5p and HMGB3 in glioma cells and tissues were analyzed using qRT-PCR. Cell proliferation was determined with colony formation and MTT assays. Cell cycle and apoptosis were examined by flow cytometry. Western blot was conducted for analyzing HMGB3, PCNA, Bax, Bcl-2, cleaved-caspase 3, Wnt-1 and β-catenin. Dual-luciferase reporter assay was measured to investigate the interaction among Circ_CLIP2, miR-195-5p and HMGB3., Results: The expression of Circ_CLIP2 and HMGB3 were increased while miR-195-5p was down-regulated in glioma cells and patients. Silencing of Circ_CLIP2 inhibited cell proliferation, enhanced cell apoptosis and inhibited the Wnt/β-catenin signaling pathway. Circ_CLIP2 suppressed miR-195-5p expression by directly sponging miR-195-5p. MiR-195-5p inhibited HMGB3 expression via directly targeting HMGB3. Knockdown of miR-195-5p facilitated cell proliferation, inhibited cell apoptosis and activated Wnt/β-catenin signaling, which were reversed by silencing of HMGB3., Conclusion: Knockdown of Circ_CLIP2 suppresses glioma progression by targeting miR-195-5p/HMGB3 thus inhibiting Wnt/β-catenin signaling. This study may provide potential therapeutic targets against glioma., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

GBM (glioblastoma multiforme) is the most malignant form of glioma and is the most commonly occurring primary malignant brain tumour. GBM is difficult to completely excise, resulting in an extremely high recurrence rate. The occurrence of an aggressive glioma phenotype depends on EMT (epithelial-mesenchymal transformation), in which epithelial cells transform into mesenchymal cells by losing their cell-cell adhesion and polarity. NcRNAs (non-coding RNAs) play a significant role in the cellular progression from a normal phenotype to a cancerous phenotype. Recently, many studies have shown that there are two essential regulatory ncRNAs, miRNAs (microRNAs) and lncRNAs, which are closely related to EMT. In this review, we conducted a comprehensive investigation of the dysregulated lncRNAs and miRNAs in gliomas with particular attention to the function and regulatory mechanisms of several important lncRNAs and miRNAs, and we discussed their roles as glioma diagnostic and prognostic biomarkers and their potential clinical applications as therapeutic targets., (Copyright © 2019. Published by Elsevier GmbH.)

Purpose: Intricate signaling networks and transcriptional regulators translate pathogen recognition into defense responses. The aim of this study was to identify the weighted genes involved in diabetic retinopathy (DR) in different rodent models of diabetes., Methods: We performed a gene coexpression analysis of publicly available microarray data, namely, the GSE19122 dataset from the Gene Expression Omnibus database. We conducted gene coexpression analysis on the microarray data to identify modules of functionally related coexpressed genes that are differentially expressed in different rodent models. We leveraged a richly curated expression dataset and used weighted gene coexpression network analysis to construct an undirected network. We screened 30 genes in the most closely related module. A protein-protein interaction network was constructed for the genes in the most related module using the Search Tool for the Retrieval of Interacting Genes. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for the 30 genes., Results: Five visual perception-related genes (Pde6g, Guca1a, Rho, Sag, and Prph2) were significantly upregulated. Based on the competing endogenous RNA hypothesis, a link between the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and visual perception-related mRNAs was constructed using bioinformatics tools. Six potential microRNAs (miR-155-5p, miR-1a-3p, miR-122-5p, miR-223-3p, miR-125b-5p, and miR-124-3p) were also screened., Conclusions: MALAT1 might play important roles in DR by regulating Sag and Guca1a through miR-124-3p and regulating Pde6g through miR-125b-5p.

Derived from brain glial cells, gliomas are currently the most common primary tumours in the central nervous system and are characterised by a high recurrence rate and poor prognosis. RWDD3 (RWD domain-containing sumoylation enhancer, also termed RSUME), which can be induced by cellular stress, such as CoCl2, heat shock and hypoxia, may play a crucial role in tumour angiogenesis, growth and metastasis. MicroRNAs (miRNAs) have been demonstrated to act as negative regulators of post-transcriptional gene expression and are involved in tumour growth and metastasis. In the present study, we explored the role of RWDD3 in glioma cell proliferation and invasion by the knockdown of RWDD3 with lentiviral shRNA and demonstrated that miRNA hsa-miR-375, regulates RWDD3 and has an important role in glioma progression. We found that expression of RWDD3 in high-grade gliomas was significantly higher than that noted in normal brain tissues and lower-grade gliomas in vivo. Knockdown of RWDD3 effectively led to cell cycle arrest, decreased proliferation and invasion, and increased apoptosis in human glioma cell lines. Furthermore, miR-375 was downregulated in human gliomas and overexpression of miR-375 caused downregulation of RWDD3 in glioma cells as well as inhibited their motility. Thus, these findings suggest that RWDD3 and miR-375 may function as therapeutic biomarkers for glioma patients.