Department of Urology Surgery, Shenzhen University General Hospital (Shenzhen University Medical Academy), China.
Department of Plastic Surgery, The First Affiliated Hospital, and Clinical Medicine College of Henan University of Science and Technology, China.
Biomed Pharmacother. 2019 Sep;117:109109. doi: 10.1016/j.biopha.2019.109109. Epub 2019 Jun 20.
Prostate carcinoma may develop into metastatic castration-resistant prostate carcinoma (mCRPC) after endocrine therapy. Exosomal microRNAs play an important role in the regulation of tumor microenvironment. Our study aimed to investigate the effect of exosomal miR-26a on tumor phenotype of prostate carcinoma. Low-grade prostate carcinoma cell line (LNCAP) and mCRPC cell line (PC-3) were treated as experimental subjects according to their miR-26a expressions. Wound healing, transwell and colony-forming unit assays were performed after miR-26a mimic/inhibitor transfection. Then, exosomes were isolated from LNCAP and PC-3 cells, and the levels of exosomal miR-26a were determined. After co-culture of LNCAP (PC-3) cells with PC-3 (LNCAP) exosomes, changes in malignant behaviors were measured. Moreover, LNCAP/PC-3 exosomes were injected into xenograft tumor mice to determine effects of the exosomes on tumorigenicity of LNCAP and PC-3 cells. MiR-26a showed a potently inhibitory effect on cell proliferation, migration and invasion of LNCAP and PC-3 cells. LNCAP exosomes had a higher miR-26a level, compared with PC-3 exosomes. Overexpression of miR-26a attenuated the enhanced malignant behavior of LNCAP cells induced by PC-3 exosomes, and miR-26a inhibition could reverse the inhibitory effects of LNCAP exosomes on PC-3 cells. Exosomal miR-26a could significantly alter the expressions of epithelial-mesenchymal transition (EMT)-related factors. Moreover, LNCAP exosomes suppressed the tumorigenicity of PC-3 cells, while PC-3 exosomes could promote the tumorigenicity of LNCAP cells. Our data suggest that exosomal miR-26a derived from prostate carcinoma cells had a suppressive effect on the metastasis and tumor growth of prostate carcinoma.
前列腺癌在经过内分泌治疗后可能发展为转移性去势抵抗性前列腺癌（mCRPC）。外泌体 microRNAs 在调节肿瘤微环境方面发挥着重要作用。本研究旨在探讨外泌体 miR-26a 对前列腺癌细胞表型的影响。根据 miR-26a 的表达，将低级别前列腺癌细胞系（LNCAP）和 mCRPC 细胞系（PC-3）作为实验对象。转染 miR-26a 模拟物/抑制剂后，进行划痕愈合、Transwell 和集落形成单位测定。然后，从 LNCAP 和 PC-3 细胞中分离外泌体，并测定外泌体 miR-26a 的水平。将 LNCAP（PC-3）细胞与 PC-3（LNCAP）外泌体共培养后，测量恶性行为的变化。此外，将 LNCAP/PC-3 外泌体注入异种移植肿瘤小鼠中，以确定外泌体对 LNCAP 和 PC-3 细胞致瘤性的影响。miR-26a 对 LNCAP 和 PC-3 细胞的增殖、迁移和侵袭有很强的抑制作用。与 PC-3 外泌体相比，LNCAP 外泌体具有更高的 miR-26a 水平。miR-26a 的过表达减弱了 PC-3 外泌体诱导的 LNCAP 细胞恶性行为增强，而 miR-26a 的抑制可以逆转 LNCAP 外泌体对 PC-3 细胞的抑制作用。外泌体 miR-26a 可显著改变上皮-间充质转化（EMT）相关因子的表达。此外，LNCAP 外泌体抑制了 PC-3 细胞的致瘤性，而 PC-3 外泌体可促进 LNCAP 细胞的致瘤性。我们的数据表明，前列腺癌细胞来源的外泌体 miR-26a 对前列腺癌的转移和肿瘤生长具有抑制作用。
