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LncRNA NOP14-AS1 Promotes Tongue Squamous Cell Carcinoma Progression by Targeting MicroRNA-665/HMGB3 Axis

Authors Li J, Fan S, Liu S, Yang G, Jin Q, Xiao Z

Received 21 November 2020

Accepted for publication 4 February 2021

Published 26 March 2021 Volume 2021:13 Pages 2821—2834

DOI https://doi.org/10.2147/CMAR.S293322

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Chien-Feng Li


Jiayi Li,1 Shuxia Fan,2 Shuang Liu,3 Guang Yang,3 Qingsong Jin,3 Zhen Xiao3

1Department of Stomatology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161000, People’s Republic of China; 2Department of Stomatology, Qiqihaer Eye & ENT Hospital, Qiqihar, Heilongjiang, 161000, People’s Republic of China; 3Department of Stomatology, The First Hospital of Qiqihar (The Affiliated Qiqihar Hospital of Southern Medical University), Qiqihar, Heilongjiang, 161000, People’s Republic of China

Correspondence: Zhen Xiao
Department of Stomatology, The First Hospital of Qiqihar (The Affiliated Qiqihar Hospital of Southern Medical University), 30 Gongyuan Road, Qiqihar, Heilongjiang 161000, People’s Republic of China
Email [email protected]

Purpose: The expression profile, clinical effects, and detailed roles of NOP14 antisense RNA 1 (NOP14-AS1) in tongue squamous cell carcinoma (TSCC) remain ambiguous and need to be further explored. Thus, this work was initiated to offer further solid evidence regarding the expression and roles of NOP14-AS1 in TSCC. Furthermore, additional efforts were exerted to reveal the molecular events by which NOP14-AS1 affects the malignant behaviours of TSCC.
Methods: NOP14-AS1 expression was detected in TSCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction. Cell Counting Kit-8 assay, flow cytometric analysis, Transwell migration and invasion assays, and xenograft tumor model analysis were performed to assess the malignant biological behaviors of TSCC cells after NOP14-AS1 depletion. Mechanistic studies were performed using bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation, and rescue experiments.
Results: NOP14-AS1 upregulation was identified in TSCC tissues and cell lines. Patients with TSCC exhibiting a high NOP14-AS1 expression faced shorter overall survival than those with a low NOP14-AS1 expression. Functionally, NOP14-AS1 depletion facilitated apoptosis and impeded cell proliferation, migration, and invasion in TSCC. In vivo, the growth of TSCC cells was hindered by NOP14-AS1 depletion. Mechanically, NOP14-AS1 functioned as a competing endogenous RNA by sponging microRNA-665 (miR-665), thereby overexpressing the target high mobility group box 3 (HMGB3) of miR-665. Lastly, rescue experiments confirmed that the introduction of HMGB3 overexpression plasmid or miR-665 inhibitor could abrogate the inhibition of aggressive phenotypes triggered by NOP14-AS1 knockdown.
Conclusion: NOP14-AS1 executed pro-oncogenic activities in TSCC cells by targeting the miR-665/HMGB3 axis. The NOP14-AS1/miR-665/HMGB pathway may be a valuable prognostic indicator and therapeutic target for preventing TSCC.

Keywords: NOP14-AS1, tongue squamous cell carcinoma, high mobility group box 3, cancer therapy

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