Department of Spine Surgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.
Department of Ultrasound, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.
Hum Cell. 2021 Mar;34(2):598-606. doi: 10.1007/s13577-020-00472-1. Epub 2021 Jan 5.
Recently, the role of miR-30a in tumor development has attracted extensive attention. In this study, we aimed to elucidate the role of miR-30a and its associated target low-density lipoprotein receptor-related protein 6 (LRP6) in clear cell renal cell carcinoma (ccRCC) cells. Here, miR-30a was markedly down-regulated in ccRCC tissues and cells, and was correlated with the advanced TNM stage and poor prognosis. By contrast, LRP6 protein level was increased in ccRCC specimens and cell lines, and inversely correlated with miR-30a expression. Stable overexpression of miR-30a suppressed cell proliferation in vitro, impeded tumor growth in vivo, prevented migration and invasion, and triggered apoptosis of ccRCC cells. Also, over-expression of miR-30a in ccRCC cells promoted the expression of the epithelial marker E-cadherin and reduced the levels of mesenchymal markers. Mechanistically, the dual-luciferase reporter, RNA immunoprecipitation and western blot assays confirmed that miR-30a directly targeted the 3'-untranslated regions of LRP6 to inhibit its expression. Further, miR-30a-mediated effect was partially reversed by co-transfection with LRP6 plasmids or enhanced by silencing of LRP6. In conclusion, miR-30a exhibits effective antitumor properties by targeting LRP6 in proliferation and metastasis of ccRCC. This study could provide new insights into the treatment of ccRCC.
最近，miR-30a 在肿瘤发展中的作用引起了广泛关注。在这项研究中，我们旨在阐明 miR-30a 及其相关靶基因低密度脂蛋白受体相关蛋白 6（LRP6）在透明细胞肾细胞癌（ccRCC）细胞中的作用。研究发现，miR-30a 在 ccRCC 组织和细胞中明显下调，与晚期 TNM 分期和不良预后相关。相比之下，LRP6 蛋白水平在 ccRCC 标本和细胞系中增加，与 miR-30a 表达呈负相关。稳定过表达 miR-30a 可抑制体外细胞增殖，阻碍体内肿瘤生长，抑制迁移和侵袭，并触发 ccRCC 细胞凋亡。此外，过表达 miR-30a 可促进 ccRCC 细胞中上皮标志物 E-钙黏蛋白的表达，并降低间充质标志物的水平。机制研究表明，双荧光素酶报告基因、RNA 免疫沉淀和 Western blot 实验证实 miR-30a 可直接靶向 LRP6 的 3'-UTR 来抑制其表达。进一步的研究发现，LRP6 质粒共转染可部分逆转 miR-30a 的作用，而 LRP6 沉默则增强了 miR-30a 的作用。综上所述，miR-30a 通过靶向 LRP6 抑制 ccRCC 的增殖和转移，发挥有效的抗肿瘤作用。该研究为 ccRCC 的治疗提供了新的思路。
