Department of Integrative Oncology, Fudan University Shanghai Cancer Center, No.270 DongAn Road, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Biol Direct. 2023 Jan 11;18(1):1. doi: 10.1186/s13062-023-00356-y.
Pancreatic cancer (PC) is a highly lethal malignancy that requires effective novel therapies. M2 macrophages are abundant in the PC microenvironment and promote cancer progression. Exosomes are emerging mediators of the crosstalk between cancer cells and the microenvironment. This study was conducted to explore the role of M2 macrophage-derived exosomes in PC.
Exosomes derived from M2 macrophages were extracted. miR-193b-3p and TRIM62 were overexpressed or silenced to examine their function in PC. Luminescence assays were used to investigate the interaction between miR-193b-3p and TRIM62. Cell proliferation was examined by EdU staining. Would healing and transwell assays were applied to evaluate cell migration and invasion. Co-immunoprecipitation was used to assess the interaction between TRIM62 and c-Myc. Gene and protein expressions were analyzed by quantitative RT-PCR and immunoblotting, respectively.
M2 macrophage-derived exosomal miR-193b-3p promoted the proliferation, migration, invasion, and glutamine uptake of SW1990 cells. Mechanism study revealed that TRIM62 is a target of miR-193b-3p. TRIM62 inhibited the proliferation, migration, invasion, and glutamine uptake of SW1990 cells by promoting c-Myc ubiquitination. Our data also suggested that TRIM62 expression negatively correlated with miR-193b-3p and c-Myc expression. High-expression of miR-193b-3p and c-Myc predicts poor prognosis, whereas low-expression of TRIM62 predicts poor prognosis in patients with PC.
M2 macrophage-derived exosomal miR-193b-3p enhances the proliferation, migration, invasion, and glutamine uptake of PC cells by targeting TRIM62, resulting in the decrease of c-Myc ubiquitination. This study not only reveals the mechanism underlying the crosstalk between M2 macrophages and PC cells but also suggests a promising therapeutic target for PC.
胰腺癌（PC）是一种高度致命的恶性肿瘤，需要有效的新型治疗方法。M2 巨噬细胞在 PC 微环境中丰富，并促进癌症进展。外泌体是癌细胞与微环境之间串扰的新兴介质。本研究旨在探讨 M2 巨噬细胞衍生的外泌体在 PC 中的作用。
提取 M2 巨噬细胞衍生的外泌体。过表达或沉默 miR-193b-3p 和 TRIM62 以研究它们在 PC 中的功能。发光测定法用于研究 miR-193b-3p 和 TRIM62 之间的相互作用。EdU 染色用于检测细胞增殖。伤口愈合和 Transwell 测定用于评估细胞迁移和侵袭。免疫沉淀用于评估 TRIM62 和 c-Myc 之间的相互作用。通过定量 RT-PCR 和免疫印迹分别分析基因和蛋白表达。
M2 巨噬细胞衍生的外泌体 miR-193b-3p 促进了 SW1990 细胞的增殖、迁移、侵袭和谷氨酰胺摄取。机制研究表明，TRIM62 是 miR-193b-3p 的靶标。TRIM62 通过促进 c-Myc 泛素化来抑制 SW1990 细胞的增殖、迁移、侵袭和谷氨酰胺摄取。我们的数据还表明，TRIM62 表达与 miR-193b-3p 和 c-Myc 表达呈负相关。miR-193b-3p 和 c-Myc 的高表达预示着 PC 患者的预后不良，而 TRIM62 的低表达预示着预后不良。
M2 巨噬细胞衍生的外泌体 miR-193b-3p 通过靶向 TRIM62 增强 PC 细胞的增殖、迁移、侵袭和谷氨酰胺摄取，从而减少 c-Myc 泛素化。本研究不仅揭示了 M2 巨噬细胞与 PC 细胞之间串扰的机制，还为 PC 提供了有希望的治疗靶点。
