Research Center, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, China.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
IUBMB Life. 2020 Aug;72(8):1705-1714. doi: 10.1002/iub.2292. Epub 2020 Apr 28.
Exosomes carrying microRNAs (miRNAs) mediate cell-to-cell communication, which play important roles in cancer growth and progression. However, the roles and molecular mechanisms of the miRNAs in the exosomes from carcinoma-associated fibroblasts (CAFs) are still not clear. The miRNA array showed that miR-3613-3p was an upregulated miRNA in CAFs exosomes. It was verified that miR-3613-3p was upregulated in exosomes from fibroblasts educated by TGF-β1 and the fibroblasts from breast cancer tissues. Exosomal miR-3613-3p promoted breast cancer cell proliferation and metastasis. The cellular functions showed that miR-3613-3p downregulation in the CAFs exosomes suppressed cell proliferation and metastasis in breast cancer by targeting SOCS2 expression. The clinical data showed that miR-3613-3p levels were negatively related to SOCS2 expression in breast cancer tissues. In a conclusion, the study demonstrated that activated fibroblasts exosomes with high levels of miR-3613-3p played an oncogenic role in breast cancer cell survival and metastasis, which suggested that miR-3613-3p function as a therapeutic target.
携带 microRNAs（miRNAs）的外泌体介导细胞间通讯，在癌症生长和进展中发挥重要作用。然而，癌相关成纤维细胞（CAFs）来源的外泌体中的 miRNAs 的作用和分子机制尚不清楚。miRNA 芯片显示，miR-3613-3p 是 CAFs 来源的外泌体中上调的 miRNA。研究证实，TGF-β1 诱导的成纤维细胞和乳腺癌组织中的成纤维细胞来源的外泌体中 miR-3613-3p 上调。外泌体 miR-3613-3p 促进乳腺癌细胞增殖和转移。细胞功能研究表明，CAFs 来源的外泌体中 miR-3613-3p 的下调通过靶向 SOCS2 表达抑制乳腺癌细胞的增殖和转移。临床数据显示，乳腺癌组织中 miR-3613-3p 水平与 SOCS2 表达呈负相关。综上所述，该研究表明，高表达 miR-3613-3p 的激活成纤维细胞来源的外泌体在乳腺癌细胞的存活和转移中发挥致癌作用，提示 miR-3613-3p 可作为治疗靶点。
