Department of General Surgery, Affiliated Hospital of Taishan Medical University, Taian, Shandong, China.
Eur Rev Med Pharmacol Sci. 2018 Jun;22(12):3804-3811. doi: 10.26355/eurrev_201806_15264.
MiR-381-3p plays an essential role in the progression of a variety of cancers, but its expression and role in papillary thyroid carcinoma (PTC) progression have not been investigated. The aim of this study was to investigate the expression of miR-381-3p and its function in PTC.
The expression levels of miR-381-3p and low-density lipoprotein receptor‑related protein 6 (LRP6) mRNA in PTC tissues and cell lines were measured using RT-PCR. Cell proliferation, migration and invasion were assessed by cell viability assay and transwell assay. Luciferase assays and Western blotting were performed to demonstrate miR-381-3p target gene.
We found that miR-381-3p was significantly down-regulated in PTC tissues and cell lines. In vitro assay indicated that up-regulation of miR-381-3p significantly suppressed PTC cell proliferation, migration and invasion. Moreover, luciferase reporter gene assay demonstrated that miR-381-3p could target LRP6 by binding to the 3' UTR. Western blot and Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) showed that miR-381-3p overexpression suppressed the expression of LRP6 at both mRNA and proteins levels. In addition, functional experiment confirmed that LRP6 was involved in the suppressive effect of miR-381-3p-mediated PTC on cell proliferation, migration and invasion.
Our findings suggested, for the first time, that miR-381-3p was lowly expressed in PTC tissues, and its up-regulation inhibited tumorigenesis of PTC by targeting LRP6.
miR-381-3p 在多种癌症的进展中发挥着重要作用，但它在甲状腺乳头状癌（PTC）进展中的表达和作用尚未被研究。本研究旨在探讨 miR-381-3p 在 PTC 中的表达及其功能。
采用 RT-PCR 检测 PTC 组织和细胞系中 miR-381-3p 和低密度脂蛋白受体相关蛋白 6（LRP6）mRNA 的表达水平。通过细胞活力测定和 Transwell 测定评估细胞增殖、迁移和侵袭。进行荧光素酶报告基因和 Western blot 实验以验证 miR-381-3p 的靶基因。
我们发现 miR-381-3p 在 PTC 组织和细胞系中显著下调。体外实验表明，上调 miR-381-3p 可显著抑制 PTC 细胞的增殖、迁移和侵袭。此外，荧光素酶报告基因实验表明，miR-381-3p 可通过与 3'UTR 结合靶向 LRP6。Western blot 和逆转录-定量聚合酶链反应（RT-qPCR）显示 miR-381-3p 过表达可抑制 LRP6 在 mRNA 和蛋白水平的表达。此外，功能实验证实 LRP6 参与了 miR-381-3p 抑制 PTC 细胞增殖、迁移和侵袭的作用。
本研究首次表明，miR-381-3p 在 PTC 组织中低表达，上调 miR-381-3p 通过靶向 LRP6 抑制 PTC 的肿瘤发生。
