Department of Urology, Hangzhou Hospital of Traditional Chinese Medicine, 453# Tiyuchang Road, Hangzhou, 310007, Zhejiang, China.
Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Transl Med. 2022 Aug 2;20(1):346. doi: 10.1186/s12967-022-03494-5.
Castration-resistant prostate cancer (CRPC) is a major cause of recurrence and mortality among prostate cancer (PCa) patients. Myeloid-derived suppressor cells (MDSCs) regulate castration resistance in PCa. Previously, it was shown that intercellular communication was efficiently mediated by exosomes (Exos), but the role and the mechanism of MDSC-derived Exos in CRPC progression was unclear.
In this study, the circRNA expression profiles in PC3 cells treated with MDSC-Exo and control cells were investigated using a circRNA microarray.
The data showed that circMID1 (hsa_circ_0007718) expression was elevated in PC3 cells treated with MDSC-Exo. Moreover, high circMID1 expression was found in PCa compared with benign prostatic hyperplasia (BPH) tissues and in CRPC patients compared with hormone sensitive prostate cancer (HSPC) patients. Further studies showed that MDSC-Exo accelerated PCa cell proliferation, migration, and invasion, while circMID1 deficiency inhibited MDSC-Exo-regulated CRPC progression in vitro and in vivo. Mechanistically, MDSC-derived exosomal S100A9 increased circMID1 expression to sponge miR-506-3p, leading to increased MID1 expression and accelerated tumor progression.
Together, our results showed that a S100A9/circMID1/miR-506-3p/MID1 axis existed in MDSC-Exo-regulated CRPC progression, which provided novel insights into MDSC-Exo regulatory mechanisms in CRPC progression.
去势抵抗性前列腺癌（CRPC）是前列腺癌（PCa）患者复发和死亡的主要原因。髓源抑制细胞（MDSCs）调节 PCa 的去势抵抗。先前的研究表明细胞间通讯可被外泌体（Exos）有效地介导，但 MDSC 来源的 Exos 在 CRPC 进展中的作用和机制尚不清楚。
在这项研究中，我们使用 circRNA 微阵列研究了 PC3 细胞用 MDSC-Exo 和对照细胞处理后的 circRNA 表达谱。
数据显示，MDSC-Exo 处理的 PC3 细胞中 circMID1（hsa_circ_0007718）的表达升高。此外，与良性前列腺增生（BPH）组织相比，PCa 中 circMID1 的表达较高，与激素敏感前列腺癌（HSPC）患者相比，CRPC 患者中 circMID1 的表达较高。进一步的研究表明，MDSC-Exo 加速了 PCa 细胞的增殖、迁移和侵袭，而 circMID1 缺乏抑制了 MDSC-Exo 调节的 CRPC 进展。机制上，MDSC 来源的外泌体 S100A9 增加了 circMID1 的表达，以海绵 miR-506-3p，导致 MID1 表达增加并加速肿瘤进展。
总之，我们的结果表明，S100A9/circMID1/miR-506-3p/MID1 轴存在于 MDSC-Exo 调节的 CRPC 进展中，为 MDSC-Exo 在 CRPC 进展中的调节机制提供了新的见解。
