微小 RNA-486 通过下调 TENM1 的表达，影响 ERK 和 Akt 信号通路以及甲状腺乳头状癌的上皮间质转化，抑制细胞增殖、侵袭和迁移。
MicroRNA-486 inhibits cell proliferation, invasion and migration via down-regulating the TENM1 expressions and affecting ERK and Akt signaling pathways and epithelial-to-mesenchymal transition in papillary thyroid carcinoma.
机构信息
Department of Ultrasound, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8429-8439. doi: 10.26355/eurrev_201910_19155.
OBJECTIVE
Papillary thyroid carcinoma (PTC) is one of the general thyroid malignancies. Recently, microRNAs (miRNAs) have identified as pivotal gene regulators in PTC tumorigenesis. The aim of this study was to investigate the role of miR-486 in PTC and its underlying mechanism.
PATIENTS AND METHODS
Fifty-six pairs of PTC tissue and matched normal tissue samples were collected from PTC patients who underwent surgery at our hospital from March 2015 to September 2017. Human thyroid epithelial cell line Nthy-ori3-1and PTC cell lines (BCPAP, K1, HTH83, and TPC-1) were cultured. The mRNA and protein expression level were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Additionally, the proliferation and migration abilities were checked by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method and transwell assay, respectively. Furthermore, dual-luciferase reporter assay was performed to confirm the combination of miR-486 and TENM1. Xenograft Model experiments were performed to assess the effects of miR-486 on tumor growth in vivo.
RESULTS
MiR-486 expression was significantly reduced in PTC, which was associated with the poorer clinicopathologic characteristics and overall survival (OS) of PTC patients. Moreover, miR-486 restoration in PTC cells was confirmed to markedly inhibit proliferation, invasion, and migration via the regulation of extracellular-signal-regulated kinase (ERK) and protein kinase B (Akt) signaling pathways and epithelial-mesenchymal transition (EMT). In the meantime, teneurin transmembrane protein 1 (TENM1) was identified as a direct functional target for miR-486 in PTC cells on the basis of bioinformatic analysis and luciferase reporter assays. Additionally, we also verified that miR-486 restoration could prominently repress the PTC growth in vivo.
CONCLUSIONS
MiR-486 exerted anti-tumor functions in PTC progression and served as promising biomarkers for the PTC treatment.
目的
甲状腺乳头状癌（PTC）是常见的甲状腺恶性肿瘤之一。最近，microRNAs（miRNAs）被鉴定为 PTC 肿瘤发生的关键基因调节剂。本研究旨在探讨 miR-486 在 PTC 中的作用及其潜在机制。
方法
收集 2015 年 3 月至 2017 年 9 月我院手术治疗的 56 对 PTC 组织和匹配的正常组织样本。培养人甲状腺上皮细胞系 Nthy-ori3-1 和 PTC 细胞系（BCPAP、K1、HTH83 和 TPC-1）。通过定量实时聚合酶链反应（qRT-PCR）和 Western blot 分别检测 mRNA 和蛋白表达水平。此外，通过 MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）法和 Transwell 测定分别检测增殖和迁移能力。此外，通过双荧光素酶报告实验证实 miR-486 与 TENM1 的结合。进行异种移植模型实验以评估 miR-486 对体内肿瘤生长的影响。
结果
miR-486 在 PTC 中表达显著降低，与 PTC 患者较差的临床病理特征和总生存（OS）相关。此外，通过调节细胞外信号调节激酶（ERK）和蛋白激酶 B（Akt）信号通路和上皮-间充质转化（EMT），证实 PTC 细胞中 miR-486 的恢复可显著抑制增殖、侵袭和迁移。同时，基于生物信息学分析和荧光素酶报告实验，鉴定出 teneurin 跨膜蛋白 1（TENM1）是 PTC 细胞中 miR-486 的直接功能靶标。此外，我们还验证了 miR-486 的恢复可以显著抑制体内 PTC 的生长。
结论
miR-486 在 PTC 进展中发挥抗肿瘤作用，可作为 PTC 治疗的有前途的生物标志物。
Zotero 插件