癌症诱导的转移前生态位（PMN）通过促进远处血管生成，在促进转移中发挥决定性作用。越来越多的证据表明，microRNA (miRNA) 在 PMN 形成过程中对血管生成具有显着影响，但其在胃癌 (GC) 中的具体作用和调节机制仍未得到充分探索。通过 miRNA-seq 鉴定了 miR-605-3p，并通过 qRT-PCR 进行了验证。分析其与GC临床病理特征及预后的相关性。进行功能测定以检查体外和体内的血管生成。利用RNA-seq、免疫荧光、透射电镜、纳米颗粒追踪分析、酶联免疫吸附测定、荧光素酶报告基因测定和生物信息学分析阐明相关分子机制。筛选出miR-605-3p作为可能调节血管生成的候选miRNA。 GC。 miR-605-3p 的低表达与 GC 的总生存期和无病生存期较短相关。 miR-605-3p 介导的 GC 分泌的外泌体通过调节源自 GC 细胞的外泌体一氧化氮合酶 3 (NOS3) 来调节血管生成。从机制上讲，miR-605-3p通过抑制囊泡相关膜蛋白3（VAMP3）表达来减少外泌体的分泌，并影响多囊泡体向GC细胞膜的转运。同时，miR-605-3p通过抑制细胞内NOS3的表达来降低外泌体中NOS3的水平。人脐静脉内皮细胞摄取GC细胞来源的外泌体NOS3后，一氧化氮水平升高，诱导血管生成，建立肝脏PMN，最终促进肝转移的发生。此外，血浆外泌体NOS3的高水平在临床上与GC患者的转移相关。miR-605-3p可能在调节VAMP3介导的外泌体NOS3的分泌中发挥关键作用，从而影响GC PMN的形成，从而抑制GC转移.© 2024。作者。

Cancer-induced pre-metastatic niches (PMNs) play a decisive role in promoting metastasis by facilitating angiogenesis in distant sites. Evidence accumulates suggesting that microRNAs (miRNAs) exert significant influence on angiogenesis during PMN formation, yet their specific roles and regulatory mechanisms in gastric cancer (GC) remain underexplored.miR-605-3p was identified through miRNA-seq and validated by qRT-PCR. Its correlation with the clinicopathological characteristics and prognosis was analyzed in GC. Functional assays were performed to examine angiogenesis both in vitro and in vivo. The related molecular mechanisms were elucidated using RNA-seq, immunofluorescence, transmission electron microscopy, nanoparticle tracking analysis, enzyme-linked immunosorbent assay, luciferase reporter assays and bioinformatics analysis.miR-605-3p was screened as a candidate miRNA that may regulate angiogenesis in GC. Low expression of miR-605-3p is associated with shorter overall survival and disease-free survival in GC. miR-605-3p-mediated GC-secreted exosomes regulate angiogenesis by regulating exosomal nitric oxide synthase 3 (NOS3) derived from GC cells. Mechanistically, miR-605-3p reduced the secretion of exosomes by inhibiting vesicle-associated membrane protein 3 (VAMP3) expression and affects the transport of multivesicular bodies to the GC cell membrane. At the same time, miR-605-3p reduces NOS3 levels in exosomes by inhibiting the expression of intracellular NOS3. Upon uptake of GC cell-derived exosomal NOS3, human umbilical vein endothelial cells exhibited increased nitric oxide levels, which induced angiogenesis, established liver PMN and ultimately promoted the occurrence of liver metastasis. Furthermore, a high level of plasma exosomal NOS3 was clinically associated with metastasis in GC patients.miR-605-3p may play a pivotal role in regulating VAMP3-mediated secretion of exosomal NOS3, thereby affecting the formation of GC PMN and thus inhibiting GC metastasis.© 2024. The Author(s).