CircRNA EPB41L2 inhibits tumorigenicity of lung adenocarcinoma through regulating CDH4 by miR-211-5p.

Abstract

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.

• Authors: S-J Zhang, J Ma, J-C Wu, Z-Z Hao, Y-N Zhang, Y-J Zhang
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 24 Issue 7 Pg. 3749-3760 (04 2020) ISSN: 2284-0729 [Electronic] Italy
• PMID: 32329852 (Publication Type: Journal Article, Retracted Publication)

Chemical References

• Cadherins
• Cytoskeletal Proteins
• MIRN211 microRNA, human
• Membrane Proteins
• MicroRNAs
• R-cadherin
• RNA, Circular
• erythrocyte membrane band 4.1 protein

Topics

• Adenocarcinoma of Lung (metabolism, pathology)
• Cadherins (genetics, metabolism)
• Cell Movement
• Cell Proliferation
• Cells, Cultured
• Cytoskeletal Proteins (genetics, metabolism)
• Humans
• Lung Neoplasms (metabolism, pathology)
• Membrane Proteins (genetics, metabolism)
• MicroRNAs (genetics, metabolism)
• RNA, Circular (genetics, metabolism)