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NR2F1-AS1 通过调控 miR-423-5p/SOX12 促进甲状腺乳头状癌细胞的增殖和侵袭。

NR2F1-AS1 regulated miR-423-5p/SOX12 to promote proliferation and invasion of papillary thyroid carcinoma.

机构信息

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

J Cell Biochem. 2020 Feb;121(2):2009-2018. doi: 10.1002/jcb.29435. Epub 2019 Nov 6.

Abstract

Papillary thyroid carcinoma (PTC) is an aggressive histological subtype of thyroid carcinoma (THCA), whose occurrence rate is high. The participation of long noncoding RNAs in the pathologies of cancers has attracted significant attention during the past decades. The purpose of the current study is to investigate the role of NR2F1 antisense RNA 1 (NR2F1-AS1) in PTC. The expression of NR2F1 in THCA samples was analyzed by bioinformatics tool gene expression profiling interactive analysis. Levels of NR2F1-AS1, microRNA-423-5p (miR-423-5p), and SRY-box 12 (SOX12) were evaluated by a quantitative reverse transcription-polymerase chain reaction and Western blot. The impact of NR2F1-AS1 on PTC cell proliferation and invasion was assessed by Cell Counting Kit-8, EdU, and Transwell invasion assays. The interactions among NR2F1-AS1, miR-423-5p, and SOX12 were determined by RNA immunoprecipitation and luciferase reporter assays. Consequently, we found that NR2F1-AS1 and SOX12 levels were elevated in PTC, whereas miR-423-5p was downregulated in PTC cells. Functionally, NR2F1-AS1 silence led to reduced proliferation and invasion of PTC cells. Mechanistically, NR2F1-AS1 interacted with miR-423-5p to induce SOX12 expression in PTC cells. In conclusion, the present study firstly stated that NR2F1-AS1 regulated miR-423-5p/SOX12 to promote proliferation and invasion of PTC, indicating NR2F1-AS1 as a potential novel target for the molecular-targeted therapy of PTC.

摘要

甲状腺癌(THCA)是一种侵袭性组织学亚型,其发生率较高。长链非编码 RNA 参与癌症病理学的作用在过去几十年中引起了广泛关注。本研究旨在探讨 NR2F1 反义 RNA 1(NR2F1-AS1)在甲状腺癌中的作用。通过生物信息学工具基因表达谱交互分析分析 THCA 样本中 NR2F1 的表达。通过定量逆转录-聚合酶链反应和 Western blot 评估 NR2F1-AS1、microRNA-423-5p(miR-423-5p)和 SRY 盒 12(SOX12)的水平。通过细胞计数试剂盒-8、EdU 和 Transwell 侵袭实验评估 NR2F1-AS1 对 PTC 细胞增殖和侵袭的影响。通过 RNA 免疫沉淀和荧光素酶报告基因实验确定 NR2F1-AS1、miR-423-5p 和 SOX12 之间的相互作用。结果发现,NR2F1-AS1 和 SOX12 在 PTC 中上调,而 miR-423-5p 在 PTC 细胞中下调。功能上,沉默 NR2F1-AS1 导致 PTC 细胞增殖和侵袭减少。机制上,NR2F1-AS1 与 miR-423-5p 相互作用诱导 PTC 细胞中 SOX12 的表达。综上所述,本研究首次表明 NR2F1-AS1 通过调节 miR-423-5p/SOX12 促进 PTC 的增殖和侵袭,表明 NR2F1-AS1 是 PTC 分子靶向治疗的潜在新靶点。

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