Back to Journals » International Journal of General Medicine » Volume 13

Long Non-Coding RNA LUCAT1 Promotes Progression of Thyroid Carcinoma by Reinforcing ADAM10 Expression Through Sequestering microRNA-493

Authors Xiong G, Chen J, Wu Z, He S, Lian M, Fang J

Received 22 July 2020

Accepted for publication 11 September 2020

Published 14 October 2020 Volume 2020:13 Pages 847—860

DOI https://doi.org/10.2147/IJGM.S273461

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Scott Fraser


Guofeng Xiong,1,2 Jiaming Chen,1 Zhen Wu,1 Shizhi He,1 Meng Lian,1 Jugao Fang1

1Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People’s Republic of China; 2Department of Otolaryngology, Head and Neck Surgery, Wenzhou Central Hospital, Wenzhou 325000, People’s Republic of China

Correspondence: Meng Lian; Jugao Fang Department of Otorhinolaryngology
Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, No. 8 Chongwenmen Inner Street, Dongcheng District (East District), Beijing 100730, People’s Republic of China
Tel/Fax +86-010-58266699
Email lianmeng_3@163.com; jugaofang03162@163.com

Background: Long non-coding RNA (lncRNA) LUCAT1 has recently been recognized as an oncogene in several malignancies. This study was launched to probe its role in thyroid carcinoma (TC) development and the implicated molecules.
Methods: LUCAT1 expression in TC cell lines and in normal thyroid follicular epithelial cell line Nthy-ori3-1 was determined by RT-qPCR. Binding relationships between LUCAT1 and microRNA (miR)-493, and between miR-493 and a disintegrin and metalloproteinase-10 (ADAM10) were predicted on a bioinformatics system and then validated through luciferase reporter gene assays. Expression of miR-493 and ADAM10 in TC cells was determined. Gain- and loss-of functions of LUCAT1, miR-493 and ADAM10 were performed to explore their influences on the behaviors of TC cells. Xenograft tumors were induced in nude mice for in vivo studies.
Results: LUCAT1 and ADAM10 were highly expressed, while miR-493 was poorly expressed in TC cell lines. LUCAT1 served as a miR-493 sponge to upregulate ADAM10 expression. Silencing of LUCAT1 discouraged proliferation, invasion, and migration but triggered apoptosis of TC cells. By contrast, these changes were abrogated by further miR-493 inhibition or ADAM10 upregulation. The in vitro experiment results were reproduced in vivo. In addition, miR-493 inhibition or ADAM10 overexpression was found to increase the phosphorylation of STAT3 in cells.
Conclusion: This study evidenced that LUCAT1 increases ADAM10 expression through sequestering miR-493, leading to JAK-STAT activation and TC cell growth and metastasis. LUCAT1 and ADAM10 may serve as therapeutic targets for TC treatment.

Keywords: long non-coding RNA LUCAT1, microRNA-493, ADAM10, thyroid carcinoma, JAK-STAT signaling pathway

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]