The expression of microRNA 21 (miR-21) has been reported to be upregulated in various types of cancer, including malignant gliomas. However, its functions and mechanisms in glioma remain to be fully elucidated. The present study established miRNA‑21 overexpression and knockdown cell lines using SRY‑box 2 (Sox2) small interfering RNA (siRNA) to knockdown expression and Sox2 cDNA was cloned into pcDNA 3.1 mammalian expression vector for ectopic expression. BIO and XAV‑939 were used for β‑catenin signaling activation and knockdown, respectively. Transwell chambers were used to assay the capacity of cells to migrate. The present study determined that increased expression of miR‑21 significantly promoted the migration and invasion of glioma cells, which was accompanied by an upregulated expression of the Sox2 protein. Sox2 overexpression also promoted glioma cell migration and invasion, whereas Sox2 siRNA markedly reduced the miR‑21‑enhanced migration and invasion of glioma cells, indicating Sox2 may act as a crucial mediator of miR‑21 function. Furthermore, miR‑21 also upregulated the protein expression level of β‑catenin, whereas anti‑miR‑21 and Sox2 knockdown significantly reduced β‑catenin expression. BIO, a β‑catenin specific agonist, enhanced migration and invasion of glioma cells. XAV‑939, an inhibitor of β‑catenin signaling, markedly inhibited the migration and invasion of glioma cells, suggesting that β‑catenin may be associated with miR‑21‑ and Sox2‑induced invasion of glioma cells. Notably, BIO restored the migration and invasion potential of glioma cells, which were inhibited by Sox2 siRNA and anti‑miR‑21. These findings indicated that β‑catenin may be an important downstream mediator of miR‑21 and Sox2. Therefore, the present study identified the miR‑21/Sox2/β‑catenin signaling pathway, which may regulate the migration and invasion of human glioma cells.

Ischemic stroke (IS) is one of the leading causes of disability and mortality worldwide. This study aims to find the crucial exosomal miRNAs associated with IS by using bioinformatics methods, reveal potential biomarkers for IS, and investigate the association between the identified biomarker and immune cell pattern in the peripheral blood of IS patients. In this study, 3 up-regulated miRNAs (hsa-miR-15b-5p, hsa-miR-184, and hsa-miR-16-5p) miRNAs in the serum exosomes between IS patients and healthy controls from GEO database (GSE199942) and 25 down-regulated genes of peripheral blood mononuclear cells of IS patients from GSE22255 were obtained with the help of the R software. GO annotation and KEGG pathway enrichment analysis showed that the 25 down-regulated genes were associated with coenzyme metabolic process and were mainly enriched in the N-glycan biosynthesis pathway. Furthermore, we performed the LASSO algorithm to narrow down the above 25 intersected genes, and identified 8 key genes which had a good diagnostic value in discriminating IS patients from the healthy controls analyzed with ROC curve. CIBERSORT algorithm indicated that the abundance of M0 macrophages and resting mast cells was significantly lower than that of the control group. The spearman correlation analysis showed that STT3A was negatively correlated with the proportion of follicular helper T cells, activated NK cells and resting dendritic cells. Finally, GSE117064 showed that has-miR-16-5p was more advantageous for diagnosing stroke. In conclusion, hsa-miR-15b-5p, hsa-miR-184, and hsa-miR-16-5p are identified as specific related exosomal miRNAs for IS patients. These genes may provide new targets for the early identification of IS.

Glioblastoma (GBM) harbors a highly inflammatory microenvironment driven predominantly by activated innate immune cells, despite being classified as an immunologically cold tumor due to limited T cell infiltration. Tumor-associated macrophages (TAMs) are key contributors to disease progression, in part through their production of interleukin-1β (IL-1β), a pro-inflammatory cytokine with tumor-promoting functions. However, the precise role of IL-1β⁺ TAMs in GBM remains incompletely understood. This study aimed to elucidate the functional contributions of IL-1β⁺ TAMs to GBM malignancy and to explore their therapeutic relevance. Single-cell RNA sequencing (scRNA-seq) analysis revealed that IL-1β⁺ TAMs were enriched in GBM tissues compared to normal brain tissue, with their elevated infiltration correlating with aggressive tumor phenotypes and poor prognosis. Functionally, IL-1β stimulated GBM cells to secrete inflammatory mediators such as PGE2 and TNFα. These mediators, in turn, upregulated C/EBPβ expression in macrophages, thereby enhancing IL-1β transcription. Mechanistically, tumor-derived PGE2 and TNFα synergistically activated C/EBPβ via EP4 receptor signaling, initiating a self-sustaining IL-1β-PGE2/TNFα-EP4-C/EBPβ-IL-1β feedback loop that amplified pro-inflammatory crosstalk between GBM cells and TAMs. Disruption of PGE2/EP4 signaling effectively suppressed IL-1β+ TAM generation and attenuated tumor growth in preclinical models. Our finding highlights how GBM cells induce macrophages to secrete IL-1β through the synergistic action of PGE2 and TNFα via the EP4 receptor and C/EBPβ activation. This feedback loop between tumor cells and macrophages fosters a pro-inflammatory TME that drives GBM progression. Targeting the PGE2/EP4-C/EBPβ signaling axis may therefore present a promising immunotherapeutic strategy to disrupt tumor-TAM crosstalk and suppress GBM progression.