Identification of a circRNA-miRNA-mRNA regulatory network for exploring novel therapeutic options for glioma

Abstract

Background Glioma is the most common brain neoplasm with a poor prognosis. Circular RNA (circRNA) and their associated competing endogenous RNA (ceRNA) network play critical roles in the pathogenesis of glioma. However, the alteration of the circRNA-miRNA-mRNA regulatory network and its correlation with glioma therapy haven’t been systematically analyzed. Methods With GEO, GEPIA2, circBank, CSCD, CircInteractome, mirWalk 2.0, and mirDIP 4.1, we constructed a circRNA–miRNA–mRNA network in glioma. LASSO regression and multivariate Cox regression analysis established a hub mRNA signature to assess the prognosis. GSVA was used to estimate the immune infiltration level. Potential anti-glioma drugs were forecasted using the cMap database and evaluated with GSEA using GEO data. Results A ceRNA network of seven circRNAs (hsa_circ_0030788/0034182/0000227/ 0018086/0000229/0036592/0002765), 15 miRNAs(hsa-miR-1200/1205/1248/ 1303/3925-5p/5693/581/586/599/607/640/647/6867-5p/767-3p/935), and 46 mRNAs (including 11 hub genes of ARHGAP11A, DRP2, HNRNPA3, IGFBP5, IP6K2, KLF10, KPNA4, NRP2, PAIP1, RCN1, and SEMA5A) was constructed. Functional enrichment showed they influenced majority of the hallmarks of tumors. Eleven hub genes were proven to be decent prognostic signatures for glioma in both TCGA and CGGA datasets. Forty-six LASSO regression significant genes were closely related to immune infiltration. Finally, five compounds (fulvestrant, tanespimycin, mifepristone, tretinoin, and harman) were predicted as potential treatments for glioma. Among them, mifepristone and tretinoin were proven to inhibit the cell cycle and DNA repair in glioma. Conclusion This study highlights the potential pathogenesis of the circRNA-miRNA-mRNA regulatory network and identifies novel therapeutic options for glioma.

Identification of Pseudo-R genes in Vitis vinifera and characterization of their role as immunomodulators in host-pathogen interactions

“…Subsequently, the co-expression analysis between DE Ψ-Rs, lncRNAs, and CDS was conducted for PM stress response in V. vinifera [74] . Previously, non-coding RNAs and mRNA co-expression networks with lncRNA-mRNA-miRNA based ce-analysis had been conducted in humans for pre-eclampsia indicating gained momentum in Ψ-based network interaction studies [75] . In addition, Ψ -based network associations has been widely studied in human cancers to affirm their prominent roles in immune system either as prognostic markers or as general mediators of cell survival [76] .…”

Construction of the underlying circRNA-miRNA-mRNA regulatory network and a new diagnostic model in ulcerative colitis by bioinformatics analysis

“…Ultimately, DEcircRNAs in the circRNA-miRNA-mRNA network were used to construct a new diagnostic model. The circRNA-miRNA-mRNA network regulatory network and new diagnostic model play an important role in the comprehensive analysis of gene interactions and identification of potential biomarkers that can be used for disease diagnosis, therapy, and prognosis of UC[ 15 , 16 ].…”