Department of Urology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.
Department of Otorhinolaryngology - Head and Neck Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.
Kaohsiung J Med Sci. 2021 Nov;37(11):973-982. doi: 10.1002/kjm2.12428. Epub 2021 Aug 1.
Accumulating studies have indicated that exosomal microRNAs (miRNAs/miRs) can mediate clear cell renal cell carcinoma (ccRCC) at the early stage, but the mechanisms remain to be specified. Here, we investigated the mechanism of exosomal miR-15a in ccRCC. After successful isolation of exosomes from RCC cells, we found that miR-15a was upregulated in ccRCC cells. Moreover, upregulation of miR-15a by pre-miR-15a promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition of ccRCC cells. A luciferase assay revealed that B-cell translocation gene 2 (BTG2) was a target gene of miR-15a and negatively correlated with miR-15a expression. BTG2 was poorly expressed in ccRCC, which reduced the proliferation of ccRCC cells. In addition, overexpression of BTG2 could reverse the promotive effects of miR-15a on ccRCC. Furthermore, BTG2 reduced PI3K/AKT pathway activity. Our results collectively indicated that exosomal miR-15a from RCC cells accelerated cell viability by downregulating BTG2 and promoting the activity of the PI3K/AKT signaling pathway. We demonstrated a novel mechanism by which exosomal miR-15a exerted pro-proliferatory effects on ccRCC, highlighting the potential of exosomal miR-15a as a target for ccRCC prognosis.
越来越多的研究表明，外泌体 microRNAs（miRNAs/miRs）可以在早期介导透明细胞肾细胞癌（ccRCC），但其机制尚待明确。在此，我们研究了外泌体 miR-15a 在 ccRCC 中的作用机制。成功从 RCC 细胞中分离出外泌体后，我们发现 miR-15a 在 ccRCC 细胞中上调。此外，通过 pre-miR-15a 上调 miR-15a 促进了 ccRCC 细胞的增殖、迁移、侵袭和上皮-间充质转化。荧光素酶报告基因实验显示 B 细胞易位基因 2（BTG2）是 miR-15a 的靶基因，与 miR-15a 表达呈负相关。BTG2 在 ccRCC 中低表达，降低了 ccRCC 细胞的增殖能力。此外，过表达 BTG2 可以逆转 miR-15a 对 ccRCC 的促进作用。此外，BTG2 降低了 PI3K/AKT 通路的活性。我们的研究结果表明，来自 RCC 细胞的外泌体 miR-15a 通过下调 BTG2 并促进 PI3K/AKT 信号通路的活性，加速了细胞活力。我们证明了外泌体 miR-15a 对 ccRCC 发挥促增殖作用的新机制，突出了外泌体 miR-15a 作为 ccRCC 预后靶点的潜力。
