Objective: Circular RNAs (circRNAs) can make contributions to cell proliferation, migration and invasion in lung adenocarcinoma (LUAD). Circ_Band 4.1-like protein 2 (circ_EPB41L2) was found to have anti-tumor roles in lung cancer. Herein, we investigated the roles of circ_EPB41L2 in LUAD tumorigenicity.
Patients and methods: The expression of circ_EPB41L2, microRNA (miR)-211-5p, and Cadherin-4 (CDH4) was measured using quantitative real-time polymerase chain reaction. Western blot was used to detect the levels of CDH4, Ki67, and E-cadherin. Cell proliferation, migration and invasion were examined using 3-(4,5)-dimethylthiazol(-z-y1)-3,5-di-phenyltetrazoliumbromide (MTT) assay and transwell assay, respectively. The interaction between miR-211-5p and circ_EPB41L2 or CDH4 was confirmed by Dual-Luciferase reporter assay. In vivo experiments were conducted using the murine xenograft model.
Results: Circ_EPB41L2 and CDH4 were down-regulated in LUAD tissues and cell lines. Overexpressed circ_EPB41L2 or CDH4 acted as a suppressor in the LUAD cell proliferation, invasion and migration in vitro. MiR-211-5p directly bound to circRNA_EPB41L2 and CDH4 3'-UTR, and circ_EPB41L2 indirectly regulated CDH4 expression by binding to miR-211-5p in LUAD cells. Furthermore, rescue assay showed circ_EPB41L2 played a protective role by repressing proliferation, migration and invasion through regulating CDH4 and miR-211-5p in LUAD cells. Besides, in vivo experiments indicated circ_EPB41L2 overexpression also inhibited tumor growth through regulating miR-211-5p and CDH4.
Conclusions: Circ_EPB41L2 functioned as a tumor suppressor to inhibit the proliferation, migration and invasion through regulating CDH4 by miR-211-5p in LUAD cells, suggesting a new understanding on the tumorigenesis of LUAD and novel molecular therapeutic targets.