[摘 要] 目的：探究骨髓间充质干细胞（BMSC）衍生的外泌体lncRNA PTENP1在膀胱癌进展中的功能机制。方法：采用透 射电子显微镜、纳米颗粒追踪分析及WB法检测外泌体标志蛋白的方式鉴定BMSC来源的外泌体（BMSC-Exo）。通过共聚焦显 微镜检测 BMSC-Exo被膀胱癌5637细胞内化的过程。按转染物不同，将膀胱癌5637和T24细胞随机分为以下组别：对照组、 BMSC-Exo组、BMSC OE-NC-Exo组、BMSC OE-PTENP1-Exo组、BMSC sh-NC-Exo组和BMSC sh-PTENP1-Exo组。采用CCK 8、集落形成实验评估细胞增殖水平，流式细胞术评估细胞凋亡水平，划痕愈合和Transwell实验评估细胞迁移和侵袭能力。通过 RNA下拉（Pull down）、RNA免疫沉淀（RIP）技术验证miR-17和PTENP1、A类清道夫受体5型（SCARA5）mRNA之间的靶向结合 关系。结果：qRT-PCR显示过表达PTENP1的BMSC外泌体（BMSC OE-PTENP1-Exo）显著提升膀胱癌细胞中PTENP1水平 （P < 0.01）。BMSC OE-PTENP1-Exo抑制细胞增殖（P < 0.01）、迁移（P < 0.01）和侵袭（P < 0.01），促进细胞凋亡（P < 0.01）。此 外，体内实验显示BMSC OE-PTENP1-Exo显著抑制裸鼠移植瘤生长（P < 0.01）。结论：BMS-Exo可通过递送PTENP1作为miR 17的“分子海绵”，解除miR-17对SCARA5的抑制作用，进而上调SCARA5的表达，抑制膀胱癌细胞的恶性生物学行为。

[Abstract] Objective: To investigate the functional mechanism of bone marrow mesenchymal stem cell (BMSC)-derived exosome lncRNA PTENP1 in bladder cancer progression. Methods: Exosomes from BMSC (BMSC-Exo) were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA), and WB assay for exosomal markers. The uptake of exosomes derived from BMSC by bladder cancer 5637 cells was confirmed through confocal microscopy. Based on different transfectants, bladder cancer cells (5637 and T24) were divided into groups: control group (no exosomes), BMSC-Exo group, BMSC OE-NC-Exo group, BMSC OE-PTENP1-Exo group, BMSC sh-NC-Exo group, and BMSC sh-PTENP1-Exo group, and co-cultured with respective exosomes (20 μg/mL). The evaluation of cell proliferation, apoptosis, migration, and invasion was conducted using CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays, respectively. The interactions involving miR-17 with PTENP1 and scavenger receptor class A member 5 (SCARA5) were validated using dual luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation (RIP) methods. Results: qRT-PCR showed that BMSC exosomes overexpressing PTENP1 (BMSC OE-PTENP1 Exo) significantly elevated PTENP1 levels in bladder cancer cells (P < 0.01). BMSC OE-PTENP1-Exo inhibited cell proliferation (P < 0.01), migration (P < 0.01), and invasion (P < 0.01), and promoted cell apoptosis (P < 0.01). Furthermore, in vivo experiments showed that BMSC OE-PTENP1-Exo significantly inhibited tumor growth in nude mice (P < 0.01). Conclusion: BMSC-derived exosomal PTENP1 inhibits BC progression by upregulating the expression of SCARA5 via sponging miR-17, providing a potential new therapeutic target for bladder cancer bladder cancer treatment.

[基金项目] 江苏高校“青蓝工程”项目[苏教师函〔2022〕29号；苏教师函〔2024〕14号]；淮安市自然科学研究计划（No. HAB202146）