Department of Breast and Thyroid Surgery, Liaocheng People's Hospital, Liaocheng, China.
Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5863-5873. doi: 10.26355/eurrev_201907_18329.
The current study aimed to explore the roles of miR-31 and SOX11 in papillary thyroid carcinoma (PTC).
Fifty-four paired human PTC specimens and matched normal thyroid tissues were obtained. Meanwhile, human thyroid epithelial cell Nthy-ori3-1 and PTC cells were cultured. The effects of miR-31 on PTC cell proliferation, invasion and migration were detected by cell proliferation assays and transwell assay, respectively. SOX11 expression in tissue samples was examined by immunohistochemical staining analyses (IHC). The correlation between SOX11 and miR-31 was clarified by Dual-Luciferase reporter assay. The relative mRNA and protein expression were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. In addition, the xenograft model experiments were performed.
Declined miR-31 expressions were frequently identified in PTC, leading to poorer overall survival (OS) and worse clinicopathologic features of PTC patients. Moreover, functional assays indicated that miR-31 overexpression could notably repress PTC cell proliferation, invasion and migration abilities by regulating the extracellular regulated protein kinases (ERK) and protein kinase B (Akt) signaling pathways and epithelial-mesenchymal transition (EMT). In addition, the results of the Luciferase reporter assay demonstrated that SOX11 was a direct functional target of miR-31 in PTC cells. In vivo, miR-31 restoration significantly suppressed the tumor growth of xenograft PTC models.
Our findings indicated that miR-31 exerted anti-PTC functions via targeting SOX11 and modulating the ERK and Akt signaling pathways and EMT. MiR-31 may potentially serve as a novel biomarker in future therapeutics of PTC.
本研究旨在探讨 miR-31 和 SOX11 在甲状腺乳头状癌（PTC）中的作用。
收集 54 对人 PTC 标本及其配对的正常甲状腺组织，同时培养人甲状腺上皮细胞 Nthy-ori3-1 和 PTC 细胞。通过细胞增殖实验和 Transwell 实验分别检测 miR-31 对 PTC 细胞增殖、侵袭和迁移的影响。采用免疫组织化学染色分析（IHC）检测组织样本中 SOX11 的表达。通过双荧光素酶报告基因检测明确 SOX11 和 miR-31 之间的相关性。通过定量实时聚合酶链反应（qRT-PCR）和 Western blot 检测相对 mRNA 和蛋白表达。此外，还进行了异种移植模型实验。
PTC 中 miR-31 表达水平降低，导致 PTC 患者总体生存率（OS）降低，临床病理特征较差。此外，功能分析表明，通过调节细胞外调节蛋白激酶（ERK）和蛋白激酶 B（Akt）信号通路和上皮-间充质转化（EMT），miR-31 过表达可显著抑制 PTC 细胞的增殖、侵袭和迁移能力。此外，荧光素酶报告基因检测结果表明，SOX11 是 PTC 细胞中 miR-31 的直接功能靶标。体内实验结果显示，miR-31 恢复可显著抑制异种移植 PTC 模型的肿瘤生长。
本研究结果表明，miR-31 通过靶向 SOX11 并调节 ERK 和 Akt 信号通路和 EMT 发挥抗 PTC 作用。miR-31 可能成为未来 PTC 治疗的新生物标志物。
