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Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Metastasis | Primary research

High expression of ESRP1 regulated by circ-0005585 promotes cell colonization in ovarian cancer

Authors: Guanming Deng, Xiaofang Zhou, Le Chen, Ying Yao, Junjun Li, Yun Zhang, Chenhui Luo, Lijuan Sun, Jie Tang

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Ovarian cancer is the third most common gynecological cancer in the world but the leading cause of death among gynecological malignancies. Epithelial splicing regulatory protein-1 (ESRP1), a key negative splicing regulator in epithelial-mesenchymal transition (EMT), has been proven to be overexpressed and may plays a role in epithelial ovarian cancer (EOC) progression. However, the functional roles of ESRP1 and the underlying mechanisms in this process still remain unclear.

Methods

Tumor invasion, migration, colony formation and animal experiments were used to study the malignant biological behavior of ESRP1. A vector-based system expressing circ-0005585 was established to investigate circRNA as a microRNAs sponge. RNA-Seq and cytoskeleton staining explored underlying mechanisms of ESRP1.

Results

Our results demonstrated that circ-0005585 regulates ESRP1 overexpression via sponging miR-23a/b and miR-15a/15b/16. Overexpression of ESRP1 suppresses EOC cell migration, but promotes colonization and drives a switch from mesenchymal to epithelial phenotype (MET) in association with actin cytoskeleton reorganization, mainly by alternative splicing EPB41L5 and RAC1. Furthermore, we have shown that high ESRP1 expression may be associated with immune-suppression in tumor immune microenvironment in vivo.

Conclusions

ESRP1 overexpression promotes MET status and correlates with actin cytoskeleton reorganization in EOC. ESRP1 plays an important role in EOC colonization. In addition, a miRs panel from two miR families can inhibit ESRP1, may provide an innovative approach for cancer theranostics.
Appendix
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Metadata
Title
High expression of ESRP1 regulated by circ-0005585 promotes cell colonization in ovarian cancer
Authors
Guanming Deng
Xiaofang Zhou
Le Chen
Ying Yao
Junjun Li
Yun Zhang
Chenhui Luo
Lijuan Sun
Jie Tang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01254-3

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