Long Noncoding RNA ZEB1-AS1 Downregulates miR-23a, Promotes Tumor Progression, and Predicts the Survival of Oral Squamous Cell Carcinoma Patients

Onco Targets Ther. 2021 Apr 16:14:2699-2710. doi: 10.2147/OTT.S297209. eCollection 2021.

Abstract

Background: Long non-coding RNAs (lncRNAs) are implicated in cancer-related biological processes such as cell proliferation, cell cycle progression, cell migration, cell invasion, and chemoresistance. However, the effects of the lncRNA ZEB1-AS1 on oral squamous cell carcinoma (OSCC) have not been adequately demonstrated. The aims of our current study were to explore the roles of lncRNA ZEB1-AS1 in OSCC progression to reveal the potential mechanism.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure relative ZEB1-AS1 expression levels in OSCC tissues and adjacent non-cancerous tissues. The biological functions of ZEB1-AS1 in OSCC growth and progression were identified by cell proliferation, wound healing, and in vitro transwell assays as well as in vivo xenograft model. The underlying mechanism was detected with a dual-luciferase reporter (DLR) assay.

Results: The up-regulation of ZEB1-AS1 and downregulation of miR-23a-3p (miR-23a) were found in OSCC cancer tissues. A ZEB1-AS1 knockdown remarkably suppressed in vitro cancerous, biological processes of OSCC cell lines such as cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT). The tumor growth was also inhibited by silencing ZEB1-AS1 in vivo, and a DLR assay confirmed the association between ZEB1-AS1 and miR-23a.

Conclusion: The newly identified lncRNA ZEB1-AS1 functions as a tumor promoter in OSCC through regulation of miR-23a. Based on these results, ZEB1-AS1 could be a valid molecular target for treating oral cancer.

Keywords: EMT; OSCC; lncRNA ZEB1-AS1; miR-23a.

Grants and funding

The work was funded by National Natural Science Foundation of China (81972535).