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环状 RNA 0008274 通过 AMPK/mTOR 信号通路促进甲状腺乳头状癌细胞的增殖和侵袭。

Has_circ_0008274 promotes cell proliferation and invasion involving AMPK/mTOR signaling pathway in papillary thyroid carcinoma.

机构信息

Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Dec;22(24):8772-8780. doi: 10.26355/eurrev_201812_16644.

Abstract

OBJECTIVE

Circular RNAs (circRNAs) have been known as important regulators in tumorigenesis. Whether circRNAs are involved in papillary thyroid carcinoma (PTC) requires to be determined. In the present study, we aimed to investigate the expression and function of has_circ_0008274 in PTC.

PATIENTS AND METHODS

Tissue expression of has_circ_0008274 was evaluated in Gene Expression Omnibus datasets (GSE93522). Real-time PCR assays were used to detect the expression of has_circ_0008274 in human PTC tissues and cell lines. The correlation of has_circ_0008274 expression with clinicopathological factors was statistically analyzed. The MTT assay, colony formation assay, transwell assays were performed to analyze and compare cell viability and invasion. Western blot analysis was used to quantify the expression of AMPK/mTOR signaling pathway proteins.

RESULTS

We found that has_circ_0008274 was significantly upregulated in PTC tissues, and the level of has_circ_0008274 was negatively associated with TNM stage and lymph node metastasis. Loss-of-function assay indicated that knockdown of has_circ_0008274 suppressed PTC cells proliferation and invasion in vitro. Mechanistically, has_circ_0008274 could inhibit the activation of AMPK/mTOR signaling pathway, which was demonstrated by measuring the expression levels of p-AMPK and p-mTOR.

CONCLUSIONS

These results demonstrate that increased has_circ_0008274 expression modulates has_circ_0008274 to enhance PTC cells proliferation and invasion. Has_circ_0008274/ AMPK/mTOR axis may be a novel therapeutic candidate target in PTC treatment.

摘要

目的

环状 RNA(circRNAs)已被认为是肿瘤发生的重要调节因子。circRNAs 是否参与甲状腺乳头状癌(PTC)尚待确定。本研究旨在探讨 has_circ_0008274 在 PTC 中的表达和功能。

患者和方法

在基因表达综合数据库(GSE93522)中评估 has_circ_0008274 的组织表达。实时 PCR 检测人 PTC 组织和细胞系中 has_circ_0008274 的表达。统计分析 has_circ_0008274 表达与临床病理因素的相关性。MTT 检测、集落形成实验和 Transwell 实验分析和比较细胞活力和侵袭。Western blot 分析用于定量 AMPK/mTOR 信号通路蛋白的表达。

结果

我们发现 has_circ_0008274 在 PTC 组织中显著上调,其水平与 TNM 分期和淋巴结转移呈负相关。功能丧失实验表明,has_circ_0008274 敲低抑制了 PTC 细胞在体外的增殖和侵袭。机制上,通过测量 p-AMPK 和 p-mTOR 的表达水平,表明 has_circ_0008274 可抑制 AMPK/mTOR 信号通路的激活。

结论

这些结果表明,has_circ_0008274 的表达增加可调节 has_circ_0008274 增强 PTC 细胞的增殖和侵袭。Has_circ_0008274/AMPK/mTOR 轴可能是 PTC 治疗的新的治疗靶点。

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