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下调 microR-147b 通过靶向 SOX15 抑制 Wnt/β-catenin 信号通路抑制甲状腺癌细胞的增殖和侵袭。

Downregulation of microR-147b represses the proliferation and invasion of thyroid carcinoma cells by inhibiting Wnt/β-catenin signaling via targeting SOX15.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.

Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.

出版信息

Mol Cell Endocrinol. 2020 Feb 5;501:110662. doi: 10.1016/j.mce.2019.110662. Epub 2019 Nov 21.

DOI:10.1016/j.mce.2019.110662
PMID:31760045
Abstract

microRNA-147b (miR-147b) is a newly identified tumor-related miRNA that is dysregulated in multiple cancer types. Yet, the role of miR-147b in thyroid carcinoma remains unknown. Herein, we found that miR-147b expression was upregulated in thyroid carcinoma tissues and cell lines. miR-147b inhibition decreased the proliferation, colony formation, and invasion of thyroid carcinoma cells. The tumor suppressive gene SRY-related high-mobility-group box gene 15 (SOX15) was predicted as a miR-147b target gene. SOX15 expression was markedly decreased in thyroid carcinoma tissues and inversely correlated with the miR-147b expression. SOX15 overexpression repressed the proliferation and invasion of thyroid carcinoma cells associated with downregulation of Wnt/β-catenin signaling. SOX15 knockdown abolished the miR-147b-inhibition-mediated antitumor effect. miR-147b inhibition or SOX15 overexpression retarded the tumor growth of thyroid carcinoma cells in vivo. Overall, our study suggests that miR-147b inhibition restrains the proliferation and invasion of thyroid carcinoma cells through upregulation of SOX15 and inhibition of Wnt/β-catenin signaling.

摘要

微小 RNA-147b(miR-147b)是一种新发现的与肿瘤相关的 miRNA,在多种癌症类型中失调。然而,miR-147b 在甲状腺癌中的作用尚不清楚。在此,我们发现 miR-147b 在甲状腺癌组织和细胞系中表达上调。miR-147b 抑制降低了甲状腺癌细胞的增殖、集落形成和侵袭能力。性决定区 Y 相关高迁移率族盒基因 15(SOX15)被预测为 miR-147b 的靶基因。甲状腺癌组织中 SOX15 表达明显下调,与 miR-147b 表达呈负相关。SOX15 过表达抑制 Wnt/β-catenin 信号转导,抑制甲状腺癌细胞的增殖和侵袭。SOX15 敲低消除了 miR-147b 抑制介导的抗肿瘤作用。miR-147b 抑制或 SOX15 过表达在体内减缓了甲状腺癌细胞的肿瘤生长。总的来说,我们的研究表明,miR-147b 通过上调 SOX15 和抑制 Wnt/β-catenin 信号转导来抑制甲状腺癌细胞的增殖和侵袭。

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