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circ_0005273 通过 SOX2 表达促进甲状腺癌进展。

circ_0005273 promotes thyroid carcinoma progression by SOX2 expression.

机构信息

Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, China.

Department of Otorhinolaryngology, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, China.

出版信息

Endocr Relat Cancer. 2020 Jan;27(1):11-21. doi: 10.1530/ERC-19-0381.

Abstract

Papillary thyroid carcinoma (PTC) is one of the most prevalent tumors in endocrine system. CircRNAs (circular RNAs) are widely known as critical regulators in tumorigenesis of papillary thyroid carcinoma (PTC). The present study focused on the functional investigation and potential molecular mechanism toward circ_0005273 in PTC progression. Gene Expression Omnibus datasets (GSE93522) and qRT-PCR (quantitative real-time PCR) analyses showed that circ_0005273 were upregulated in PTC tissues and cell lines. Moreover, circ_0005273 was located in the cytoplasm of PTC cells and suggested poor prognosis in PTC patients. In vivo and in vitro functional assays indicated that knockdown of circ_0005273 inhibited PTC tumor growth and progression, respectively. Mechanistically, miR-1183 was identified as functional target of circ_0005273, and circ_0005273 could directly bind to miR-1138 and relieve inhibition of SRY (sex-determining region Y)-box 2 (SOX2). Data from Cell Counting Kit-8, colony formation assays and transwell assays revealed that the oncogenic role of circ_0005273 on PTC progression dependent on miR-1183-mediated SOX2 expression. In conclusion, circ_0005273 functioned as a tumor promoter of PTC via circ_0005273/miR-1183/SOX2 axis, suggesting a novel biomarker and therapeutic target for PTC.

摘要

甲状腺乳头状癌(PTC)是内分泌系统中最常见的肿瘤之一。CircRNAs(环状 RNA)被广泛认为是甲状腺乳头状癌(PTC)发生肿瘤的关键调节因子。本研究集中于circ_0005273 在 PTC 进展中的功能研究和潜在的分子机制。基因表达综合数据库(GSE93522)和 qRT-PCR(定量实时 PCR)分析显示,circ_0005273 在 PTC 组织和细胞系中上调。此外,circ_0005273 位于 PTC 细胞的细胞质中,并提示 PTC 患者预后不良。体内和体外功能测定表明,circ_0005273 的敲低分别抑制了 PTC 肿瘤的生长和进展。机制上,miR-1183 被鉴定为 circ_0005273 的功能靶标,circ_0005273 可以直接结合 miR-1138 并减轻性别决定区 Y-盒 2(SOX2)的抑制作用。Cell Counting Kit-8、集落形成测定和 Transwell 测定的数据表明,circ_0005273 对 PTC 进展的致癌作用依赖于 miR-1183 介导的 SOX2 表达。总之,circ_0005273 通过 circ_0005273/miR-1183/SOX2 轴发挥 PTC 促进因子的作用,提示其是 PTC 的一种新的生物标志物和治疗靶点。

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