从前列腺癌（PCa）发生的第一步开始，肿瘤就与最近的脂肪组织（称为前列腺周围脂肪组织（PPAT））接触。细胞外囊泡是非编码RNA（例如对细胞通讯至关重要的miRNA）的重要载体。 PPAT 分泌的细胞外囊泡可能在脂肪细胞与肿瘤之间的相互作用中发挥关键作用。分析 PPAT 外囊泡 (EV) 衍生的 miRNA 含量对于了解肿瘤进展和侵袭性具有重要意义。总共使用了 24 个人类 PPAT 样本和 17 个膀胱周围脂肪组织 (PVAT) 样本。通过蛋白质印迹和透射电子显微镜（TEM）对 EV 进行表征，并通过共聚焦显微镜验证 PCa 细胞的摄取。 PPAT 和 PVAT 外植体培养过夜，分离 EV，并分析 miRNA 含量表达谱。进行通路和功能富集分析以寻找潜在的 miRNA 靶标。使用 PCa 细胞系、miRNA 抑制剂和靶基因沉默剂评估体外功能研究。Western blot 和 TEM 揭示了源自 PPAT (PPAT-EV) 样品的 EV 的特征。提取 EV 并在 PCa 细胞的细胞质中发现。 PPAT 和 PVAT 样品之间有 9 个 miRNA 存在差异表达。 RORA 基因（RAR 相关孤儿受体 A）被确定为 9 条 miRNA 调控途径的共同靶标。体外功能分析显示，RORA 基因受 PPAT-EVs 衍生的 miRNA 调节，并被发现与细胞增殖和炎症有关。肿瘤前列腺周围脂肪组织与 PCa 肿瘤侵袭性相关，可以设想新的治疗策略。© 2024。作者。

From the first steps of prostate cancer (PCa) initiation, tumours are in contact with the most-proximal adipose tissue called periprostatic adipose tissue (PPAT). Extracellular vesicles are important carriers of non-coding RNA such as miRNAs that are crucial for cellular communication. The secretion of extracellular vesicles by PPAT may play a key role in the interactions between adipocytes and tumour. Analysing the PPAT exovesicles (EVs) derived-miRNA content can be of great relevance for understanding tumour progression and aggressiveness.A total of 24 samples of human PPAT and 17 samples of perivesical adipose tissue (PVAT) were used. EVs were characterized by western blot and transmission electron microscopy (TEM), and uptake by PCa cells was verified by confocal microscopy. PPAT and PVAT explants were cultured overnight, EVs were isolated, and miRNA content expression profile was analysed. Pathway and functional enrichment analyses were performed seeking potential miRNA targets. In vitro functional studies were evaluated using PCa cells lines, miRNA inhibitors and target gene silencers.Western blot and TEM revealed the characteristics of EVs derived from PPAT (PPAT-EVs) samples. The EVs were up taken and found in the cytoplasm of PCa cells. Nine miRNAs were differentially expressed between PPAT and PVAT samples. The RORA gene (RAR Related Orphan Receptor A) was identified as a common target of 9 miRNA-regulated pathways. In vitro functional analysis revealed that the RORA gene was regulated by PPAT-EVs-derived miRNAs and was found to be implicated in cell proliferation and inflammation.Tumour periprostatic adipose tissue is linked to PCa tumour aggressiveness and could be envisaged for new therapeutic strategies.© 2024. The Author(s).