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长链非编码 RNA TUG1 通过靶向 miR-145 影响甲状腺乳头状癌细胞的增殖、迁移和 EMT 形成。

LncRNA TUG1 influences papillary thyroid cancer cell proliferation, migration and EMT formation through targeting miR-145.

机构信息

Department of Radiation Oncology, The Second Hospital of Dalian Medical University, Dalian 116027, China.

Department of Otolaryngology, Dalian Jinzhou First People's Hospital, Dalian 116027, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2017 Jul 1;49(7):588-597. doi: 10.1093/abbs/gmx047.

Abstract

LncRNA TUG1, a tumor oncogene associated with various human cancers, has been reported to be involved in regulating various cellular processes, such as proliferation, apoptosis and invasion through targeting multiple genes. However, its biological function in thyroid cancer cells has not been elucidated. The aim of this study is to measure TUG1 expression level and evaluate its function in thyroid cancer cells. LncRNA TUG1 expression levels in thyroid cancer tissues and three thyroid cancer cell lines (the ATC cell lines SW1736 and KAT18 and the FTC cell line FTC133) were assessed by qRT-PCR and compared with that of the human normal breast epithelial cell HGC-27. MTT assay, colony formation assay, transwell assay and western blot analysis were performed to assess the effects of TUG1 on proliferation, metastasis and EMT formation in thyroid cancer cells in vitro. Rescue assay was performed to further confirm that TUG1 contributes to the progression of thyroid cancer cells through regulating miR-145/ZEB1 signal pathway. LncRNA TUG1 was found to be up-regulated in thyroid cancer tissues and thyroid cancer cells compared with that in the human normal breast epithelial cell HGC-27. Increased lncRNA TUG1 expression was found to significantly promote tumor cell proliferation, and facilitate cell invasion, while down-regulated TUG1 could obviously inhibit cell proliferation, migration/invasion and reverse EMT to MET. These results indicated that TUG1 may contribute to the progression of thyroid cancer cells by function as a ceRNA competitive sponging miR-145, and that lncRNA TUG1 is associated with tumor progression in thyroid cancer cells.

摘要

LncRNA TUG1,一种与多种人类癌症相关的肿瘤癌基因,据报道可通过靶向多个基因参与调节多种细胞过程,如增殖、凋亡和侵袭。然而,其在甲状腺癌细胞中的生物学功能尚未阐明。本研究旨在测量 TUG1 的表达水平并评估其在甲状腺癌细胞中的功能。通过 qRT-PCR 评估甲状腺癌组织和三种甲状腺癌细胞系(ATC 细胞系 SW1736 和 KAT18 以及 FTC 细胞系 FTC133)中的 TUG1 表达水平,并与正常人乳腺上皮细胞 HGC-27 进行比较。MTT 测定、集落形成测定、Transwell 测定和 Western blot 分析用于评估 TUG1 对甲状腺癌细胞体外增殖、转移和 EMT 形成的影响。通过挽救实验进一步证实 TUG1 通过调节 miR-145/ZEB1 信号通路促进甲状腺癌细胞的进展。与正常人乳腺上皮细胞 HGC-27 相比,在甲状腺癌组织和甲状腺癌细胞中发现 lncRNA TUG1 上调。发现增加的 lncRNA TUG1 表达可显著促进肿瘤细胞增殖,并促进细胞侵袭,而下调的 TUG1 可明显抑制细胞增殖、迁移/侵袭并逆转 EMT 至 MET。这些结果表明,TUG1 可能通过作为 ceRNA 竞争性吸附 miR-145 来促进甲状腺癌细胞的进展,并且 lncRNA TUG1 与甲状腺癌细胞中的肿瘤进展有关。

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