Circular RNA circMMP1 Contributes to the Progression of Glioma Through Regulating TGIF2 Expression by Sponging miR-195-5p

Zhang, Kuiming; Wang, Qi; Zhao, D; Liu, Zhen

doi:10.1007/s10528-021-10119-x

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…[37] Zhang et al certificate that MMP1 expression increased in glioma and that knockdown of the MMP1 expression is followed by a reduction in the invasive ability of glioma. [38] And MMP1 promotes the metastasis of pancreatic cancer and ovarian cancer. [39,40] There is still no literature on the specific role of LAMB4 in glioma, but in gastric and colon cancers, researchers have found that LAMB4 mutations may promote the development of tumors.…”

Section: Discussionmentioning

confidence: 99%

The value of basement membrane-associated genes in the prognosis and immune regulation of glioma

Sun,

Li,

Chen

et al. 2023

Medicine

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Gliomas have a high incidence rate in central nervous tumors. Although many breakthroughs have been made in the pathogenesis and treatment of glioma, the recurrence and metastasis rates of patients have not been improved based on the uniqueness of glioma. Glioma destroys the surrounding basement membrane (BM), leading to local infiltration, resulting in the corresponding clinical and neurological symptoms. Therefore, exploring the biological roles played by BM associated genes in glioma is particularly necessary for a comprehensive understanding of the biological processes of glioma and its treatment. Differential expression and univariate COX regression analyses were used to identify the basement membrane genes (BMGs) to be included in the model. LASSO regression was used to construct the BMG model. The Kaplan–Meier (KM) survival analysis model was used to assess the prognosis discrimination between training sets, validation sets, and clinical subgroups. Receiver-operating characteristic (ROC) analysis was used to test the prognostic efficacy of the model. Use calibration curves to verify the accuracy of nomograms. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and gene set enrichment analysis (GSEA) were used to analyze the function and pathway enrichment among the model groups. ESTIMATE and other 7 algorithms including CIBERSORT were used to evaluate the immune microenvironment. “pRRophetic” was used to evaluate drug sensitivity. This study demonstrated that high-risk genes (LAMB4, MMP1, MMP7) promote glioma progression and negatively correlate with patient prognosis. In the tumor microenvironment (TME), high-risk genes have increased scores of macrophages, neutrophils, immune checkpoints, chemokines, and chemokine receptors. This study suggests that BMGs, especially high-risk-related genes, are potential sites for glioma therapy, a new prospect for comprehensively understanding the molecular mechanism of glioma.

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Section: Discussionmentioning

confidence: 99%

The value of basement membrane-associated genes in the prognosis and immune regulation of glioma

Sun,

Li,

Chen

et al. 2023

Medicine

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“…Additionally, TGIF2 is associated with the epithelialmesenchymal transition (EMT) phenotype in various diseases, including lung adenocarcinoma (12), primary biliary cholangitis (13), chronic obstructive pulmonary disease (14), colon cancer (15), prostate cancer (16), hepatocellular carcinoma (17) etc. Notably, as a downstream target of multiple non-coding RNAs, TGIF2 regulates the progression of glioma (18)(19)(20)(21). Previous in vitro experiments have suggested that TGIF2 promotes the EMT phenotype and migration in U87MG and A172 glioma cells (21), indicating the potential involvement of TGIF2 in regulating glioma cell invasion and tumor metastasis.…”

Section: Introductionmentioning

confidence: 99%

TGIF2 is a potential biomarker for diagnosis and prognosis of glioma

Zhang,

Dong

et al. 2024

Front. Immunol.

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BackgroundTGFB-induced factor homeobox 2 (TGIF2), a member of the Three-Amino-acid-Loop-Extension (TALE) superfamily, has been implicated in various malignant tumors. However, its prognostic significance in glioma, impact on tumor immune infiltration, and underlying mechanisms in glioma development remain elusive.MethodsThe expression of TGIF2 in various human normal tissues, normal brain tissues, and gliomas was investigated using HPA, TCGA, GTEx, and GEO databases. The study employed several approaches, including Kaplan-Meier analysis, ROC analysis, logistic regression, Cox regression, GO analysis, KEGG analysis, and GSEA, to explore the relationship between TGIF2 expression and clinicopathologic features, prognostic value, and potential biological functions in glioma patients. The impact of TGIF2 on tumor immune infiltration was assessed through Estimate, ssGSEA, and Spearman analysis. Genes coexpressed with TGIF2 were identified, and the protein-protein interaction (PPI) network of these coexpressed genes were constructed using the STRING database and Cytoscape software. Hub genes were identified using CytoHubba plugin, and their clinical predictive value was explored. Furthermore, in vitro experiments were performed by knocking down and knocking out TGIF2 using siRNA and CRISPR/Cas9 gene editing, and the role of TGIF2 in glioma cell invasion and migration was analyzed using transwell assay, scratch wound-healing assay, RT-qPCR, and Western blot.ResultsTGIF2 mRNA was found to be upregulated in 21 cancers, including glioma. High expression of TGIF2 was associated with malignant phenotypes and poor prognosis in glioma patients, indicating its potential as an independent prognostic factor. Furthermore, elevated TGIF2 expression positively correlated with cell cycle regulation, DNA synthesis and repair, extracellular matrix (ECM) components, immune response, and several signaling pathways that promote tumor progression. TGIF2 showed correlations with Th2 cells, macrophages, and various immunoregulatory genes. The hub genes coexpressed with TGIF2 demonstrated significant predictive value. Additionally, in vitro experiments revealed that knockdown and knockout of TGIF2 inhibited glioma cell invasion, migration and suppressed the epithelial-mesenchymal transition (EMT) phenotype.ConclusionTGIF2 emerges as a potential biomarker for glioma, possibly linked to tumor immune infiltration and EMT.

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“…Consolidating our target mRNA predictions from TargetScan and miRDB platforms established a list of 192 putative mmu-let-7b-5p mRNA targets showing increased abundance during infection, including Integrin Beta 3 subunit (Itgb3, Log2 FC = 2.35), Argonaute RISC Catalytic Component 2 (Ago2, Log2 FC = 1.37), Dual-specificity phosphatase 9 (Dusp9, Log2 FC = 1.94) (Figure2A) and 7 mRNAs encoding for transcription factors (TFs) or epigenetic regulators (ERs), i.e. Arid3a, E2f6, Hmga1, Klf8, Nr6a1, Pbx1, and Zfp202 (Figure2B), which are involved in regulation of proliferation regulation, cell differentiation, DNA structure modification, and cancer-related signaling pathways(Trimarchi et al 2001, Patterson et al 2008, Wang et al 2022, Guo et al 2023, Bai et al 2024, Kao et al 2024, Zhang et al 2024.…”

mentioning

confidence: 99%

MAPPING CHANGES OF MIRNA-MRNA NETWORKS INLEISHMANIA-INFECTEDMACROPHAGES PREDICTS REGULATORY MIRNA-TF LOOPS AS NOVEL TARGETS OF PARASITE IMMUNE SUBVERSION

Gharsallah,

Lecoeur,

Varet

et al. 2024

Preprint

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MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level and play a crucial role in numerous disease processes, including infections. Although intracellular microbial pathogens are known to modulate host cell gene expression to establish permissive conditions for infection, the specific role of host-encoded miRNAs underlying such subversion remains poorly understood. In this study, we employed the protozoan parasite Leishmania amazonensis as a model system to investigate how infection of macrophages modifies the host cell miRNA profile to evade antimicrobial functions and to establish permissive conditions for intracellular proliferation. Dual RNA-seq analyses using matched mRNA and miRNA-enriched samples from uninfected and L. amazonensis-infected bone marrow-derived macrophages (BMDMs) revealed 102 differentially expressed miRNAs (padj<0.05), with 18 miRNAs showing reduced and 84 miRNAs showing increased abundance in infected BMDMs. Mapping putative networks of miRNA-mRNA interactions based on the observed expression changes, combined with Gene Ontology enrichment analyses, allowed us to identify potential miRNA target genes involved in key biological processes and metabolic pathways that permit parasite intracellular survival and proliferation. Our analyses predict the existence of a large miRNA-mRNA network affecting the expression level of numerous transcription factors that indicates inhibition of the NF-κB-dependent inflammatory response or the promotion of cholesterol biosynthesis during infection. In particular, the over 10e3-fold increase in the abundance of mmu-miR-686 in infected BMDMs was correlated with a reduced abundance of putative target transcripts implicated in miRNA biogenesis itself, in RNA binding, and in regulation of apoptosis, such as Caspase 12, the mRNA decay activator protein Zfp36l1 or Leukemia Inhibitory Factor Receptor Alpha. Likewise, the over 200-fold increase in abundance of mmu-miR-6546-3p was associated with a reduced abundance of putative target mRNAs implicated in cytokine-mediated signaling, positive regulation of apoptotic process and regulation of gene expression, affecting, for example, the MADS box transcription enhancer factor 2, the transformation related protein 53 inducible nuclear protein 1, or the G protein-coupled receptor 35. Interestingly, both miRNAs are predicted to simultaneously target 32 mRNAs that showed reduced abundance in infected BMDMs, including Maturin Neural Progenitor Differentiation Regulator (Mturn), a regulator of NF-κB transcription factor activity. In conclusion, our approach provides novel insight into molecular mechanisms that may govern macrophage subversion and intracellular Leishmania survival. Our results shed new light on the complex relationship among miRNAs, macrophage gene expression and Leishmania infection, proposing regulatory feed-forward loops (FFLs) and feedback loops (FBLs) between miRNAs and TFs as a novel target of Leishmania immune subversion. These findings open exciting new avenues for the development of intervention strategies aimed at disrupting such crucial interactions, for example using an anti-miR (antagomir) approach against mmu-miR-686 and mmu-miR-6546-3p.

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Circular RNA circMMP1 Contributes to the Progression of Glioma Through Regulating TGIF2 Expression by Sponging miR-195-5p

Cited by 4 publications

References 36 publications

The value of basement membrane-associated genes in the prognosis and immune regulation of glioma

The value of basement membrane-associated genes in the prognosis and immune regulation of glioma

TGIF2 is a potential biomarker for diagnosis and prognosis of glioma

MAPPING CHANGES OF MIRNA-MRNA NETWORKS INLEISHMANIA-INFECTEDMACROPHAGES PREDICTS REGULATORY MIRNA-TF LOOPS AS NOVEL TARGETS OF PARASITE IMMUNE SUBVERSION

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