Wei Yongbao, Chen Zhensheng, Zhang Ruochen, Wu Bangkui, Lin Le, Zhu Qingguo, Ye Liefu, Li Tao, Li Feng
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Department of Urology, Fujian Provincial Hospital, Fuzhou, China.
J Cancer. 2022 Jul 18;13(9):2970-2981. doi: 10.7150/jca.71706. eCollection 2022.
This study explored the role of circulating exosomal microRNA-423-5p in the progression of PCa and its molecular mechanism. First, based on the microarray analysis, microRNA-423-5p was at a high expression level in PCa peripheral blood samples. It was demonstrated that microRNA-423-5p expression in serum exosomes of PCa patients was notably higher than that in healthy people as revealed by qRT-PCR. Further studies indicated that overexpressing microRNA-423-5p promoted cell progression of PCa. Microarray analysis and luciferase gene reporter assay illustrated that FRMD3 was targeted by microRNA-423-5p, and its expression was down-regulated by microRNA-423-5p. While FEMD3 knockdown would reverse the repressive effect of silencing microRNA-423-5p on PCa cell functions. In addition, it was exhibited that exosomes carrying microRNA-423-5p could internalize into PCa cells by labeling and tracing exosomes. Cell function assays and animal experiments manifested those exosomes carrying microRNA-423-5p could enhance PCa cell proliferation, migration, and invasion . In conclusion, this study indicated that blood circulating exosomal microRNA-423-5p played important roles in PCa cell functions, and illustrated the molecular mechanism of microRNA-423-5p as an oncogene in PCa.
本研究探讨了循环外泌体微小RNA-423-5p在前列腺癌进展中的作用及其分子机制。首先,基于微阵列分析,微小RNA-423-5p在前列腺癌外周血样本中呈高表达水平。qRT-PCR结果显示,前列腺癌患者血清外泌体中微小RNA-423-5p的表达明显高于健康人。进一步研究表明,过表达微小RNA-423-5p可促进前列腺癌细胞进展。微阵列分析和荧光素酶基因报告试验表明,FRMD3是微小RNA-423-5p的靶标,其表达受微小RNA-423-5p下调。而敲低FEMD3可逆转沉默微小RNA-423-5p对前列腺癌细胞功能的抑制作用。此外,通过对外泌体进行标记和追踪显示,携带微小RNA-423-5p的外泌体可内化进入前列腺癌细胞。细胞功能试验和动物实验表明,携带微小RNA-423-5p的外泌体可增强前列腺癌细胞的增殖、迁移和侵袭能力。总之,本研究表明血液循环外泌体微小RNA-423-5p在前列腺癌细胞功能中发挥重要作用,并阐明了微小RNA-423-5p作为前列腺癌致癌基因的分子机制。