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:CDC25A inhibition sensitizes melanoma cells to doxorubicin and NK cell therapy.
CDC25A inhibition sensitizes melanoma cells to doxorubicin and NK cell therapy.
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细胞分裂周期25(CDC25)磷酸酶是调节细胞周期阶段转换的关键因子,也是参与DNA损伤应答的检查点机制的重要组成部分。新证据提示,CDC25家族成员在多种癌症中具有致癌潜力。然而,其在不同癌症中的表达模式和功能尚缺乏全面研究。本研究利用多个数据库,在泛癌层面评估CDC25家族的基因表达、分子特征、诊断价值及预后价值,并重点研究黑色素瘤中CDC25A的表达及临床关联。结果显示,多数癌症中CDC25家族成员表达显著异常,并与较差预后相关;不同癌症中的CDC25家族成员还受到DNA甲基化和遗传改变的差异性调控。此外,CDC25家族在黑色素瘤恶性进展中发挥重要作用。功能研究表明,抑制CDC25A可阻止黑色素瘤细胞增殖,并使其对化疗和NK细胞治疗更敏感。总之,CDC25家族可能成为多种癌症诊断和预后的重要生物标志物,而CDC25A则是黑色素瘤有前景的治疗靶点。
Cell division cycle 25 (CDC25) phosphatases serve as crucial regulators of cell cycle phase transitions and essential components of the checkpoint machinery involved in DNA damage response. Emerging evidence indicates the oncogenic potential of CDC25 family members across various cancers.
However, comprehensive insights into the expression pattern and function of the CDC25 family in diverse cancers remain unexplored. In our study, we investigated CDC25 family using multiple databases, including gene expression levels, molecular signatures, diagnosis value, and prognostic value in pan-cancer.
Furthermore, we focused on melanoma and systematically explored CDC25A expression and its clinical correlations. As a result, the expression of CDC25 family members is significantly abnormal in most cancers, correlating with poorer prognosis. CDC25 family members are differently regulated by DNA methylation and genetic alterations across various cancers.
In addition, CDC25 family plays a critical role in the malignant progression of melanoma. Functional investigation reveals that CDC25A inhibition suppresses the proliferation of melanoma cells and sensitizes melanoma cells to chemotherapy and NK cell therapy.
In conclusion, our study suggests that CDC25 family may serve as a significant biomarker for diagnosis and prognosis across multiple cancers, with CDC25A as a promising therapeutic target for melanoma.
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