RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Prunella vulgaris: A potential molecule for the treatment of hepatocellular carcinoma.
Prunella vulgaris: A potential molecule for the treatment of hepatocellular carcinoma.
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Prunella vulgaris(PV)广泛用于治疗多种疾病,但其与肝细胞癌(HCC)的关系仍不清楚。本研究系统评估PV在HCC中的治疗潜力,并探讨其分子机制。从Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform数据库获取PV的活性化合物和分子靶点,并使用Gene Expression Omnibus数据库鉴定HCC相关靶点。构建药物-疾病靶点网络以识别关键枢纽基因,并通过免疫分析、单细胞RNA测序、分子对接和体外实验进一步研究这些基因。
我们鉴定出185个药物靶点和635个HCC相关靶点,其中15个潜在PV靶点与HCC进展相关。体外验证证实这些靶点在HCC细胞中显著表达。机制分析表明,这些枢纽基因可能通过肿瘤蛋白53信号等通路影响HCC进展,并与免疫细胞亚群相关,包括CD8+ T细胞和NK 细胞。
本研究鉴定了PV用于HCC治疗的关键生物活性成分,并揭示了其分子机制。这些靶点的失调与HCC发病机制相关,提示其作为新型生物标志物的潜力。未来研究将聚焦于进一步的体外和体内验证,以探索这些靶点的临床适用性以及PV与其他治疗联合的协同潜力。
Prunella vulgaris (PV) is widely used in treating various diseases, but its relationship with hepatocellular carcinoma (HCC) remains unclear.
This study systematically evaluates PV's therapeutic potential in HCC and explores its molecular mechanisms. Active compounds and molecular targets of PV were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and HCC-related targets were identified using the Gene Expression Omnibus database. A drug-disease target network was built to identify key hub genes, which were further investigated through immune analysis, single-cell RNA sequencing, molecular docking, and in vitro experiments.
We identified 185 drug targets and 635 HCC-related targets, with 15 potential PV targets linked to HCC progression. In vitro validation confirmed significant expression of these targets in HCC cells. Mechanistic analysis indicated that these hub genes may influence HCC progression through pathways like tumor protein 53 signaling and are associated with immune cell subsets, including CD8+ T cells and natural killer cells.
This study identifies key bioactive components of PV for HCC treatment and reveals their molecular mechanisms. Dysregulation of these targets correlates with HCC pathogenesis, suggesting their potential as novel biomarkers. Future research will focus on further validation in vitro and in vivo to explore the clinical applicability of these targets and the synergistic potential of PV in combination with other treatments.
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