Long Noncoding RNA CDKN2B-AS1 Facilitates Lung Cancer Development Through Regulating miR-378b/NR2C2

Onco Targets Ther. 2020 Oct 20:13:10641-10649. doi: 10.2147/OTT.S261973. eCollection 2020.

Abstract

Aim: Long noncoding RNA (lncRNA) have proved to be important regulators in various diseases. CDKN2B-AS1 was a newly identified tumor-related lncRNA, and previous studies have reported its function in laryngeal squamous cancer and osteosarcoma. However, the function and mechanism of lncRNA CDKN2B-AS1 in lung cancer are still unknown.

Methods: Cell proliferation, invasion, migration and apoptosis were detected via CCK-8, transwell assay and Western blot. Bioinformatics analysis was used to predict the potential target of CDKN2B-AS1. A rescue experiment was performed to identify the relationship between CDKN2B-AS1 and miR-378b.

Results: The expression of lncRNA CDKN2B-AS1 was significantly upregulated in lung cancer tissues and cell lines. Overexpression of CDKN2B-AS1 promoted cell proliferation, invasion and reduced cell apoptosis. Knockdown of CDKN2B-AS1 inhibited cell proliferation, invasion and increased cell apoptosis. Bioinformatics analysis predicted that miR-378b was the direct target. We also provided evidence that NR2C2 was the target of miR-378b. The expression of NR2C2 was significantly upregulated in lung cancer tissues and cell lines. The rescue experiment further confirmed the relationship between CDKN2B-AS1 and miR-378b. Overexpression of miR-378b completely reversed the function of CDKN2B-AS1.

Conclusion: Taken together, our results comprehensively analyzed the function of CDKN2B-AS1 in lung cancer and provided a possible mechanism that CDKN2B-AS1 facilitates lung cancer development by regulating miR-378b and NR2C2. Thus, our study offers a potential therapeutic target for treating lung cancer.

Keywords: CDKN2B-AS1; lncRNA; lung cancer.

Grants and funding

This work was supported by Henan Provincial Department of Science and Technology Research Project (172102310116).