Department of Ultrasonography, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, ErDao District, Changchun 13033, China.
Department of Radiology, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, ErDao District, Changchun 13033, China.
Biomed Pharmacother. 2017 Nov;95:1718-1724. doi: 10.1016/j.biopha.2017.09.074. Epub 2017 Oct 6.
The aims of this study were to test the influence of miR-217 on the proliferation, invasion, migration of thyroid cancer and the relevant mechanism.
miR-217 expression levels in thyroid cancer tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR).Cell Counting Kit-8, flow cytometer, wound healing, transwell invasion assays were applied to evaluate the effect of miR-217 on proliferation, apoptosis, migration and invasion of thyroid cells. The luciferase reporter assay, qRT-PCR, and western blot were used to identify target of miR-217. Relative relationship of expression level between miR-217 and AKT3 was analyzed in thyroid cancer tissues. Xenograft transplantation was performed to test effect of miR-217 in vivo.
We found that the expression of miR-217 was significantly decreased in thyroid cancer tissues cell lines. Significantly, decreased miR-217 expression were associated with the clinical stage and lymph node metastasis. Function studies revealed that miR-217 overexpression in thyroid cancer cells inhibited proliferation, migration, and invasion in vitro, as well as suppressed tumor growth in vivo. Subsequently, AKT3 was identified as a target of miR-217 in thyroid cancer. AKT3 expression was upregulated in thyroid cancer tissues, was inversely correlated with miR-217expression. Besides, overexpression of AKT3 efficiently abrogates suppressive effect on proliferation, migration and invasion in thyroid cancer cells caused by overexpression of miR-217.
These data demonstrated a tumor suppressor role for miR-217 in thyroid cancer development and progression by targeting AKT3, suggesting miR-217 might be a potential target for thyroid cancer.
本研究旨在探讨 miR-217 对甲状腺癌细胞增殖、侵袭和迁移的影响及其相关机制。
采用实时定量 PCR（qRT-PCR）检测甲状腺癌组织和细胞系中 miR-217 的表达水平。应用细胞计数试剂盒-8（CCK-8）、流式细胞术、划痕愈合实验和 Transwell 侵袭实验评估 miR-217 对甲状腺细胞增殖、凋亡、迁移和侵袭的影响。采用荧光素酶报告基因实验、qRT-PCR 和 Western blot 检测 miR-217 的靶基因。分析甲状腺癌组织中 miR-217 与 AKT3 的表达水平的相关性。通过异种移植实验检测 miR-217 在体内的作用。
我们发现 miR-217 在甲状腺癌组织和细胞系中的表达明显降低。miR-217 表达水平降低与临床分期和淋巴结转移有关。功能研究表明，甲状腺癌细胞中 miR-217 的过表达可抑制体外增殖、迁移和侵袭，并抑制体内肿瘤生长。随后，AKT3 被鉴定为甲状腺癌中 miR-217 的靶基因。甲状腺癌组织中 AKT3 的表达上调，与 miR-217 的表达呈负相关。此外，过表达 AKT3 可有效消除 miR-217 过表达对甲状腺癌细胞增殖、迁移和侵袭的抑制作用。
这些数据表明，miR-217 通过靶向 AKT3 在甲状腺癌的发生和发展中发挥肿瘤抑制作用，提示 miR-217 可能成为甲状腺癌的潜在治疗靶点。
