Department of Nuclear Medicine, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, China.
Cell Cycle. 2020 May;19(10):1105-1121. doi: 10.1080/15384101.2020.1746490. Epub 2020 Apr 19.
MicroRNAs (miRNAs) have been reported to serve pivotal roles in the regulation of papillary thyroid cancer (PTC) development; thus, the aim of this study is to identify the impact of miR-203 and AKT3 on the epithelial-mesenchymal transition (EMT), migration and invasion of PTC. MiR-203 and AKT3 expression in PTC tissues and cells were tested. TPC-1 cells and K1 cells were screened for follow-up experiments. Apoptosis-related proteins (Bcl-2 and Bax), EMT-related proteins (Vimentin and E-cadherin), proliferation-associated proteins (Ki67 and CDK4), invasion- and migration-related protein (MMP-2 and MMP-9) were verified. The effects of upregulated miR-203 and downregulated AKT3 on the biological characteristics of PTC cells in each group were detected via the gain- and loss-of-function assays. The targeting relationship between miR-203 and AKT3 was verified.MiR-203 expression declined and AKT3 heightened in PTC tissues and cells. Upregulated miR-203 and downregulated AKT3 reduced the tumor volume and weight, suppressed cell migration, colony formation, proliferation, invasion, proliferation-associated proteins (Ki67 and CDK4), invasion- and migration-related protein (MMP-2 and MMP-9) and promoted cell apoptosis, raised E-cadherin and decreased Vimentin protein expression in TPC-1 cells. On the contrary, the K1 cells with the downregulated miR-203 or upregulated AKT3 exhibited an opposite result. This study suggests that upregulated miR-203 suppresses EMT, invasion, proliferation and migration as well as induces apoptosis of PTC cells via downregulated AKT3.
微小 RNA（miRNAs）已被报道在调控甲状腺乳头状癌（PTC）发展中起关键作用；因此，本研究旨在确定 miR-203 和 AKT3 对 PTC 上皮-间充质转化（EMT）、迁移和侵袭的影响。检测了 PTC 组织和细胞中的 miR-203 和 AKT3 表达。筛选 TPC-1 细胞和 K1 细胞进行后续实验。验证了凋亡相关蛋白（Bcl-2 和 Bax）、EMT 相关蛋白（波形蛋白和 E-钙黏蛋白）、增殖相关蛋白（Ki67 和 CDK4）、侵袭和迁移相关蛋白（MMP-2 和 MMP-9）。通过功能获得和缺失实验检测了上调 miR-203 和下调 AKT3 对各组 PTC 细胞生物学特性的影响。验证了 miR-203 和 AKT3 之间的靶向关系。miR-203 在 PTC 组织和细胞中的表达降低，AKT3 表达升高。上调 miR-203 和下调 AKT3 降低了肿瘤体积和重量，抑制了细胞迁移、集落形成、增殖、侵袭、增殖相关蛋白（Ki67 和 CDK4）、侵袭和迁移相关蛋白（MMP-2 和 MMP-9），促进了细胞凋亡，提高了 TPC-1 细胞中 E-钙黏蛋白的表达，降低了波形蛋白的表达。相反，下调 miR-203 或上调 AKT3 的 K1 细胞则表现出相反的结果。本研究表明，上调的 miR-203 通过下调 AKT3 抑制 PTC 细胞的 EMT、侵袭、增殖和迁移，并诱导其凋亡。
