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Upregulation of circFLNA contributes to laryngeal squamous cell carcinoma migration by circFLNA–miR-486-3p-FLNA axis

Authors :
Jian-Xing Wang
Yan Liu
Xin-Ju Jia
Shu-Xia Liu
Jin-Hui Dong
Xiu-Min Ren
Ou Xu
Hai-Zhong Zhang
Hui-Jun Duan
Chun-Guang Shan
Source :
Cancer Cell International, Vol 19, Iss 1, Pp 1-13 (2019)
Publication Year :
2019
Publisher :
BMC, 2019.

Abstract

Abstract Background Accumulating evidence shows that circular RNAs (circRNAs) plays vital roles in tumor progression. However, the biological functions of circRNAs in laryngeal squamous cell carcinoma (LSCC) metastasis is still unclear. Methods qRT-PCR was used to detect circFLNA, miRNAs and FLNA mRNA expression. Transwell assay and western blot were performed to evaluate cell migration ability and to detect FLNA, MMP2 and MLK1 protein expression, respectively. RNA pull-down analysis was used to find the binding-miRNAs of circFLNA. Luciferase reporter assay was used to examine the effect of circFLNA on miRNAs and miR-486-3p on FLNA expression. Results In this study, we confirmed that a Filamin A (FLNA)-derived hsa_circ_0092012 known as circFLNA, was upregulated in LSCC, and the higher expression of circFLNA was correlated with LSCC lymph node metastasis. Increased circFLNA facilitates LSCC cell migration ability through upregulating FLNA and MMP2 protein expression. Mechanistically, we find that circFLNA sponges miR-486-3p in LSCC cells, relieving miR-486-3p-induced repression of FLNA which promotes LSCC cell migration. Accordingly, FLNA mRNA is overexpressed in LSCC tissues and a higher FLNA level is correlated with poor survival. Dysregulation of the circFLNA/miR-486-3p/FLNA regulatory pathway contributes to LSCC migration. Conclusions In summary, our study sheds light on the regulatory mechanism of circFLNA in LSCC migration via sponging miR‐486-3p, which downregulates the FLNA protein expression. Targeting circFLNA/miR-486-3p/FLAN axis provides a potential therapeutic target for aggressive LSCC.

Details

Language :
English
ISSN :
14752867
Volume :
19
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Cancer Cell International
Publication Type :
Academic Journal
Accession number :
edsdoj.16d3c5f82764cfb8d8ef0a03eb521b0
Document Type :
article
Full Text :
https://doi.org/10.1186/s12935-019-0924-9