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Long Non-Coding RNA TRPM2-AS Promotes Cell Migration and Invasion by Serving as a ceRNA of miR-138 and Inducing SOX4-Mediated EMT in Laryngeal Squamous Cell Carcinoma

Authors Wang N, Wang L, Pan X

Received 31 May 2020

Accepted for publication 27 July 2020

Published 25 August 2020 Volume 2020:12 Pages 7805—7812

DOI https://doi.org/10.2147/CMAR.S265412

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Harikrishna Nakshatri


Ning Wang,1,2,* Lei Wang,2,* Xinliang Pan1– 3

1Department of Otorhinolaryngology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2Department of Otolaryngology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong 266035, People’s Republic of China; 3NHC Key Laboratory of Otorhinolaryngology (Shandong University), Jinan, Shandong 250012, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xinliang Pan Department of Otorhinolaryngology
Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of China
Email panxinliangpxl2001@163.com

Background: Laryngeal squamous cell carcinoma (LSCC) is a common type of malignant tumors of larynx, and in this study, we aimed to evaluate the functional role of long non-coding RNA TRPM2-AS in LSCC.
Methods: The expression levels of TRPM2-AS in LSCC tissues and cell lines were detected by RT-qPCR analysis. In vitro functional assays, including MTT assay and transwell assay, were performed to explore the biological effects of TRPM2-AS on LSCC cells. The expression levels of EMT-relevant proteins were detected by Western blot analysis. The interaction between TRPM2-AS and miR-138 in LSCC, predicted by bioinformatic method, was verified by dual-luciferase reporter assay.
Results: We observed that TRPM2-AS was highly expressed in human LSCC tissues and cell lines. LSCC patients with advanced clinical stage exhibited higher intratumoral TRPM2-AS expression. The results of functional assays demonstrated that TRPM2-AS knockdown remarkably inhibited the proliferation, migration and invasion of LSCC cells, whereas TRPM2-AS overexpression showed opposite effects. In mechanism, we further observed that TRPM2-AS directly bound to miR-138 and served as competing endogenous RNA (ceRNA), thereby increasing SOX4 expression and promoting EMT in LSCC. The oncogenic effects of TRPM2-AS in LSCC cells were partly diminished by miR-138 restoration.
Conclusion: In short, our findings provided first evidence that TRPM2-AS is highly expressed and exerts its oncogenic role in LSCC partly by miR-138/SOX4 axis.

Keywords: laryngeal squamous cell carcinoma, long non-coding RNA TRPM2-AS, miR-138, SOX4, EMT

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