Abstract：
BACKGROUND: Exosomes play a crucial role in promoting tumor progression, dissemination, and resistance to treatment. These extracellular vesicles hold promise as valuable indicators for cancer detection. Our investigation focuses on exploring the significance and clinical relevance of exosomal miRNAs in small cell lung cancer (SCLC).
METHODS: Serum exosomes were isolated from both SCLC patients and healthy controls, and subjected to exosomal miRNA sequencing analysis. Mimics and inhibitors were employed to investigate the function of exosomal miR-1128-5p in cell migration and proliferation, both in vitro and in vivo. Western blot and luciferase assay were utilized to identify the interaction between miR-1228-5p and dual specificity phosphatase 22 (DUSP22).
RESULTS: Exosomal miRNA sequencing analysis revealed enrichment of specific miRNAs in SCLC compared to healthy controls. Circulating miR-1228-5p was upregulated in SCLC patients, associated with advanced stages, suggesting its potential oncogenic role. In vitro, miR-1228-5p expression was significantly higher in SCLC cells than in normal cells. SCLC cell-derived exosomes contained elevated levels of miR-1228-5p, facilitating its entry into co-cultured cells. Notably, migration and proliferation induced by SCLC exosomes were mainly mediated by miR-1228-5p. In vivo experiments confirmed these findings. Western blot analysis demonstrated miR-1228-5p\'s regulation of DUSP22 expression, and luciferase reporter assay validated DUSP22 as a direct target gene. Overexpressing DUSP22 counteracted miR-1228-5p\'s promotion of SCLC cell proliferation and migration.
CONCLUSIONS: Collectively, our results suggest that exosomes play a role in facilitating cancer growth and metastasis by delivering miR-1228-5p. Moreover, circulating exosomal miR-1228-5p may serve as a potential marker for SCLC diagnosis and prognosis.
METHODS: Serum exosomes were isolated from both SCLC patients and healthy controls, and subjected to exosomal miRNA sequencing analysis. Mimics and inhibitors were employed to investigate the function of exosomal miR-1128-5p in cell migration and proliferation, both in vitro and in vivo. Western blot and luciferase assay were utilized to identify the interaction between miR-1228-5p and dual specificity phosphatase 22 (DUSP22).
RESULTS: Exosomal miRNA sequencing analysis revealed enrichment of specific miRNAs in SCLC compared to healthy controls. Circulating miR-1228-5p was upregulated in SCLC patients, associated with advanced stages, suggesting its potential oncogenic role. In vitro, miR-1228-5p expression was significantly higher in SCLC cells than in normal cells. SCLC cell-derived exosomes contained elevated levels of miR-1228-5p, facilitating its entry into co-cultured cells. Notably, migration and proliferation induced by SCLC exosomes were mainly mediated by miR-1228-5p. In vivo experiments confirmed these findings. Western blot analysis demonstrated miR-1228-5p\'s regulation of DUSP22 expression, and luciferase reporter assay validated DUSP22 as a direct target gene. Overexpressing DUSP22 counteracted miR-1228-5p\'s promotion of SCLC cell proliferation and migration.
CONCLUSIONS: Collectively, our results suggest that exosomes play a role in facilitating cancer growth and metastasis by delivering miR-1228-5p. Moreover, circulating exosomal miR-1228-5p may serve as a potential marker for SCLC diagnosis and prognosis.
摘要：
背景：外泌体在促进肿瘤进展中起着至关重要的作用，传播,和对治疗的抵抗力。这些细胞外囊泡有望作为癌症检测的有价值的指标。我们的研究重点是探索外泌体miRNA在小细胞肺癌（SCLC）中的意义和临床意义。
方法：从SCLC患者和健康对照中分离血清外泌体，并进行外泌体miRNA测序分析。模拟和抑制剂用于研究外泌体miR-1128-5p在细胞迁移和增殖中的功能。在体外和体内。使用蛋白质印迹和荧光素酶测定来鉴定miR-1228-5p与双特异性磷酸酶22(DUSP22)之间的相互作用。
结果：外泌体miRNA测序分析显示，与健康对照相比，SCLC中特定miRNA的富集。循环miR-1228-5p在SCLC患者中上调，与高级阶段相关，提示其潜在的致癌作用。体外，miR-1228-5p在SCLC细胞中的表达显著高于正常细胞。SCLC细胞来源的外泌体含有升高水平的miR-1228-5p，促进其进入共培养细胞。值得注意的是,SCLC外泌体诱导的细胞迁移和增殖主要由miR-1228-5p介导。体内实验证实了这些发现。Westernblot分析显示miR-1228-5p调节DUSP22表达，和荧光素酶报告基因分析验证了DUSP22作为直接靶基因。过表达DUSP22抑制miR-1228-5p促进SCLC细胞增殖和迁移。
结论：总的来说，我们的结果表明,外泌体通过递送miR-1228-5p在促进癌症生长和转移中发挥作用.此外，循环外泌体miR-1228-5p可作为SCLC诊断和预后的潜在标志物.
方法：从SCLC患者和健康对照中分离血清外泌体，并进行外泌体miRNA测序分析。模拟和抑制剂用于研究外泌体miR-1128-5p在细胞迁移和增殖中的功能。在体外和体内。使用蛋白质印迹和荧光素酶测定来鉴定miR-1228-5p与双特异性磷酸酶22(DUSP22)之间的相互作用。
结果：外泌体miRNA测序分析显示，与健康对照相比，SCLC中特定miRNA的富集。循环miR-1228-5p在SCLC患者中上调，与高级阶段相关，提示其潜在的致癌作用。体外，miR-1228-5p在SCLC细胞中的表达显著高于正常细胞。SCLC细胞来源的外泌体含有升高水平的miR-1228-5p，促进其进入共培养细胞。值得注意的是,SCLC外泌体诱导的细胞迁移和增殖主要由miR-1228-5p介导。体内实验证实了这些发现。Westernblot分析显示miR-1228-5p调节DUSP22表达，和荧光素酶报告基因分析验证了DUSP22作为直接靶基因。过表达DUSP22抑制miR-1228-5p促进SCLC细胞增殖和迁移。
结论：总的来说，我们的结果表明,外泌体通过递送miR-1228-5p在促进癌症生长和转移中发挥作用.此外，循环外泌体miR-1228-5p可作为SCLC诊断和预后的潜在标志物.
