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Background: Hepatocellular carcinoma (HCC), which has high rates of recurrence and metastasis and is the main reason and the most common tumor for cancer mortality worldwide, has an unfavorable prognosis. N7-methylguanosine (m7G) modification can affect the formation and development of tumors by affecting gene expression and other biological processes. In addition, many previous studies have confirmed the unique function of long noncoding RNAs (lncRNAs) in tumor progression; however, studies exploring the functions of m7G-related lncRNAs in HCC patients has been limited. Methods: Relevant RNA expression information was acquired from The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov), and m7G-related lncRNAs were identified via gene coexpression analysis. Afterward, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate regression analyses were implemented to construct an ideal risk model whose validity was verified using Kaplan-Meier survival, principal component, receiver operating characteristic (ROC) curve, and nomogram analyses. In addition, the potential functions of lncRNAs in the novel signature were explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA). At last, in both risk groups and subtypes classified based on the expression of the risk-related lncRNAs, we analyzed the immune characteristics and drug sensitivity of patients. Results: After rigorous screening processes, we built a model based on 11 m7G-related lncRNAs for predicting patient overall survival (OS). The results suggested that the survival status of patients with high-risk scores was lower than that of patients with low-risk scores, and a high-risk score was related to malignant clinical features. Cox regression analysis showed that the m7G risk score was an independent prognostic parameter. Moreover, immune cell infiltration and immunotherapy sensitivity differed between the risk groups. Conclusion: The m7G risk score model constructed based on 11 m7G-related lncRNAs can effectively assess the OS of HCC patients and may offer support for making individualized treatment and immunotherapy decisions for HCC patients.
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BACKGROUND: Several studies have demonstrated that mesenchymal stem cells can ameliorate the inflammation of allergic rhinitis (AR) and correct the Th1/Th2 immune imbalance. METHODS: This study was performed to explore the immunomodulation properties of stem cells from human exfoliated deciduous teeth (SHEDs) in the treatment of AR in vivo and in vitro. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection, and then SHEDs or bone marrow mesenchymal stem cells (BMMSCs) were injected intravenously before challenge. We evaluated nasal symptoms, inflammatory infiltration of nasal mucosa, immunoglobulin secretion, cytokine production, and mRNA expression in the spleen. In addition, peripheral blood mononuclear cells (PBMCs) from AR patients were cultured with SHEDs or BMMSCs in the presence of phytohemagglutinin (PHA). PBMCs cultured alone with or without PHA served as controls. After 3 days of culture, we examined the effect of SHEDs on T lymphocyte proliferation, cytokine secretion, and the proportion of Foxp3+ Treg cells via flow cytometry. Finally, to determine the role of soluble factors (TGF-ß1, PGE2) in the immunomodulatory mechanism, a cytokine neutralization assay was performed. RESULTS: Nasal symptoms and inflammatory infiltration were significantly reduced after SHED administration. The OVA-specific IgE and IgG1 levels in serum were significantly decreased, and the increased IL-4, IL-5, IL-13, and IL-17A levels in the spleen after OVA challenge were markedly downregulated, while the level of IFN-γ was upregulated by SHED administration. The mRNA expression levels also changed correspondingly. SHEDs significantly inhibited the proliferation of T lymphocytes; increased the levels of IFN-γ, IL-10, PGE2, and TGF-ß1; decreased the levels of IL-4 and IL-17A; and induced the expansion of Treg cells in the coculture system. The neutralization of TGF-ß1 partly relieved the immunosuppression of SHEDs, but blocking PGE2 did not. In addition, SHEDs were superior to BMMSCs in inhibiting the Th2 immune response in vivo and inducing the expansion of Treg cells in vitro. CONCLUSION: These results suggest that SHEDs could correct the CD4+ T cell immune imbalance via Treg cells and may be potential therapeutic agents for the treatment of allergic diseases, such as AR, in the future.