Cancer Management and Research (Aug 2020)
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
Abstract
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 workCorrespondence: Xinliang Pan Department of OtorhinolaryngologyQilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of ChinaEmail [email protected]: 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
