LncRNA ZFAS1 promotes invasion of medullary thyroid carcinoma by enhancing EPAS1 expression via miR-214-3p/UCHL1 axis

IF 3.6 3区生物学 Q3 CELL BIOLOGY

Journal of Cell Communication and Signaling Pub Date : 2024-04-12 DOI:10.1002/ccs3.12021

Wenjing Chen, Shaoqing Wang, Dongmei Wei, Lili Zhai, Li Liu, Chunlei Pan, Zhongshu Han, Huiming Liu, Wei Zhong, Xin Jiang

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Abstract

lncRNA ZFAS1 was identified to facilitate thyroid cancer, but its role in medullary thyroid carcinoma (MTC) remains unknown. This study aimed to unravel the potential function of this lncRNA in MTC by investigating the involvement of the lncRNA ZFAS1 in a ceRNA network that regulates MTC invasion. Proliferation, invasion, and migration of cells were evaluated using EdU staining and Transwell assays. Immunoprecipitation (IP) assays, dual-fluorescence reporter, and RNA IP assays were employed to examine the binding interaction among genes. Nude mice were used to explore the role of lncRNA ZFAS1 in MTC in vivo. ZFAS1 and EPAS1 were upregulated in MTC. Silencing ZFAS1 inhibited MTC cell proliferation and invasion under hypoxic conditions, which reduced EPAS1 protein levels. UCHL1 knockdown increased EPAS1 ubiquitination. ZFAS1 positively regulated UCHL1 expression by binding to miR-214-3p. Finally, silencing ZFAS1 significantly repressed tumor formation and metastasis in MTC. LncRNA ZFAS1 promotes invasion of MTC by upregulating EPAS1 expression via the miR-214-3p/UCHL1 axis.

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LncRNA ZFAS1通过miR-214-3p/UCHL1轴增强EPAS1的表达，从而促进甲状腺髓样癌的侵袭

已发现lncRNA ZFAS1可促进甲状腺癌的发生，但它在甲状腺髓样癌中的作用仍不清楚。本研究旨在通过研究lncRNA ZFAS1参与调控MTC侵袭的ceRNA网络，揭示该lncRNA在MTC中的潜在功能。利用EdU染色和Transwell试验评估了细胞的增殖、侵袭和迁移。免疫沉淀（IP）试验、双荧光报告和 RNA IP 试验被用来检测基因之间的结合相互作用。利用裸鼠探讨了 lncRNA ZFAS1 在 MTC 中的体内作用。ZFAS1和EPAS1在MTC中上调。沉默ZFAS1可抑制缺氧条件下MTC细胞的增殖和侵袭，从而降低EPAS1蛋白水平。UCHL1敲除增加了EPAS1的泛素化。ZFAS1通过与miR-214-3p结合正向调节UCHL1的表达。最后，沉默 ZFAS1 能显著抑制 MTC 肿瘤的形成和转移。LncRNA ZFAS1通过miR-214-3p/UCHL1轴上调EPAS1的表达，从而促进MTC的侵袭。

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来源期刊

Journal of Cell Communication and Signaling CELL BIOLOGY-

CiteScore

6.40

自引率

4.90%

发文量

期刊介绍： The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.