CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Suppressive function of bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-187 in prostate cancer.
骨髓间充质干细胞来源外泌体(BMSC-exos)在癌症治疗中的应用已被广泛研究。
骨髓间充质干细胞来源外泌体(BMSC-exos)在癌症治疗中的应用已被广泛研究。在此,我们阐述了携带microRNA-187(miR-187)的BMSC-exos在前列腺癌中的功能。通过微阵列分析筛选差异表达的miR和基因。评估了前列腺癌中CD276与miR-187之间的关系。在转染miR-187模拟物/抑制剂或CD276过表达后,分析了它们在前列腺癌细胞生物学过程中的作用。随后将前列腺癌细胞暴露于经miR-187模拟物/抑制剂或CD276过表达处理的BMSC-exos,以明确外泌体miR-187的体外和体内效应。在前列腺癌中,miR-187低表达,而CD276显著上调。此外,恢复miR-187通过靶向CD276抑制了前列腺癌细胞的恶性特性。miR-187上调导致CD276表达及JAK3-STAT3-Slug信号通路下降。接下来,携带miR-187的BMSC-exos有助于抑制细胞恶性特征以及限制致瘤性和肿瘤转移。总之,本研究表明,BMSC来源的外泌体miR-187通过降低CD276/JAK3-STAT3-Slug轴来抑制前列腺癌。
Application of bone marrow-derived mesenchymal stem cell-derived exosomes (BMSC-exos) in cancer treatment has been widely studied. Here, we elaborated the function of BMSC-exos containing microRNA-187 (miR-187) in prostate cancer. Differentially expressed miRs and genes were screened with microarray analysis. The relationship between CD276 and miR-187 in prostate cancer was evaluated. Following miR-187 mimic/inhibitor or CD276 overexpression transfection, their actions in prostate cancer cell biological processes were analyzed. Prostate cancer cells were then exposed to BMSC-exos that were treated with either miR-187 mimic/inhibitor or CD276 overexpression for pinpointing the in vitro and in vivo effects of exosomal miR-187. miR-187 was poorly expressed while CD276 was significantly upregulated in prostate cancer. Additionally, restoring miR-187 inhibited the prostate cancer cell malignant properties by targeting CD276. Upregulation of miR-187 led to declines in CD276 expression and the JAK3-STAT3-Slug signaling pathway. Next, BMSC-exos carrying miR-187 contributed to repressed cell malignant features as well as limited tumorigenicity and tumor metastasis. Collectively, this study demonstrated that BMSC-derived exosomal miR-187 restrained prostate cancer by reducing CD276/JAK3-STAT3-Slug axis.
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