FZD1/KLF10-hsa-miR-4762-5p/miR-224-3p-circular RNAs axis as prognostic biomarkers and therapeutic targets for glioblastoma: a comprehensive report

Abstract

Background The circular RNA (circRNA) plays a vital role in the pathogenesis of tumors as a competitive endogenous RNA (ceRNA). Given the high aggressiveness and fatality rate of glioblastoma (GBM) as well as poor prognosis, it is necessary to construct a circRNA-related ceRNA network for further studies on the mechanism of GBM and identify possible biomarkers as well as therapeutic drugs. Methods Three datasets from the gene expression omnibus (GEO) database were downloaded to distinguish differential circRNAs, microRNAs, and messenger RNAs respectively in GBM. With the help of GEPIA2, circBank, CSCD, TargetScan, miRDB, and miRTarBase databases, we established a circRNAs-related ceRNA network in GBM. Functional enrichments were employed to profile the most relevant mRNAs to indirectly clarify the mechanisms of the ceRNA network. Based on the expression profile data and survival information of GBM patients from the GEO and the cancer genome atlas (TCGA) databases, we performed survival analysis to select prognostic mRNAs and constructed a novel circRNA-miRNA-mRNA central regulatory subnetwork. The DGIdb database was used to find potential drug–gene interactions. Results The datasets obtained from the GEO and TCGA databases were analyzed, and 504 differentially expressed mRNAs (DEmRNAs), 71 differentially expressed microRNAs (DEmiRNAs), and 270 differentially expressed circRNAs (DEcircRNAs) were screened out. The novel ceRNA regulatory network included 22 circRNAs, 11 miRNAs, and 15 mRNAs. FZD1 and KLF10 were significantly correlated with the overall survival rate of patients with GBM (P < 0.05). The final survival subnetwork contained six circRNAs, two miRNAs, and two mRNAs. Two small-molecule compounds and one antibody could be used as therapeutic drugs for GBM. Interestingly, the Wnt signaling pathway appeared in both KEGG and GO functional terms. Conclusions Results of this study demonstrate that FZD1 and KLF10 may exert regulatory functions in GBM, and the ceRNA-mediated network could be a therapeutic strategy for GBM.

Urine Proteomic Signatures of Mild Hypothermia Treatment in Cerebral Ischemia–Reperfusion Injury in Rats

“…FZD1, the initial member of the frizzled gene family, encodes seven transmembrane proteins that function as receptors for the Wnt signaling pathway (Jia et al 2023 ). In the context of hippocampal development, FZD1 exhibits varying levels of expression (Mardones et al 2016 ).…”

A Prediction Model for Deciphering Intratumoral Heterogeneity Derived from the Microglia/Macrophages of Glioma Using Non-Invasive Radiogenomics

“…IFNGR2, the receptor for interferon-gamma, plays a dual role in immune response modulation and is associated with the polarization of microglia and macrophages within the glioma microenvironment, influencing immunogenicity and the efficacy of immunotherapies [35,36]. KLF10, a transcription factor, is implicated in the regulation of TGF-β signaling, a pathway known for its contribution to the immunosuppressive milieu [37][38][39]. PLAUR, or urokinase receptor, is instrumental in extracellular matrix remodeling, a process integral to tumor invasion and angiogenesis.…”

Artificial intelligence utility for drug development: ChatGPT and beyond

“…Here, we examined the capacity, efficiency, and value of ChatGPT to provide information relevant to drug development. We chose to ask mostly questions requesting information relevant to the development of novel antidepressant drugs, including tentative nucleotide‐based therapeutics, a topic of wide interest (Jordheim et al, 2013; Kamel et al, 2023; Li et al, 2022; Müller et al, 2017); as well as microRNA therapeutics (Carrella et al, 2022; Duan et al, 2023; Jia et al, 2023). We are aware that the examples of our questions and the ChatGPT replies shown in the Supporting Information: File represent a tiny fraction of the multifaceted aspects of drug development, or the IT capacities of ChatGPT.…”