Dataset Information

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

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.

SUBMITTER: Deng G

PROVIDER: S-EPMC7236301 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Deng Guanming G Zhou Xiaofang X Chen Le L Yao Ying Y Li Junjun J Zhang Yun Y Luo Chenhui C Sun Lijuan L Tang Jie J

Cancer cell international 20200519

<h4>Background</h4>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.<h4 ...[more]

PMID: 32467669

Similar Datasets

Project description:BackgroundEpithelial ovarian cancer (EOC) is the most common ovarian malignant cancer. Circular RNA is a type of endogenous noncoding RNA and is considered as a novel regulatory molecule in the development and progression of tumors. This study investigated the expression and functions of a circular RNA, circular-phosphoglycerate mutase 1 (circ-PGAM1), in EOC tissues and cells.MethodsThe expression of circ-PGAM1 and miR-542-3p in EOC was analyzed using quantitative RT-PCR. Immunohistochemistry and western blot were performed to confirm the localization and expression of cell division cycle 5-like (CDC5L) and pseudopodium enriched atypical kinase 1 (PEAK1) in EOC tissues. Cell lines (CAOV3 and OVCAR3) overexpressing or silencingcirc-PGAM1 and miR-542-3p were established to explore the functions of circ-PGAM1 and miR-542-3p in ovarian cancer cells. Furthermore, dual-luciferase reporter assay was performed to study the interactions between circ-PGAM1 and miR-542-3p and between miR-542-3p and CDC5L. CCK-8, transwell, and flow cytometry were used to study the effect of circ-PGAM1 and miR-542-3p on cell biological behaviors including proliferation, migration, invasion, and apoptosis. The interaction between CDC5L and the PEAK1 gene promoter was confirmed using chromatin immunoprecipitation (ChIP).ResultsCirc-PGAM1 was upregulated in EOC tissues, whereas linear PGAM1 was not deregulated in EOC tissues. Silencing of circ-PAGM1 inhibited proliferation, migration, and invasion of ovarian cancer cells and promoted cell apoptosis. MiR-542-3p was downregulated in EOC tissues, and miR-542-3p overexpression inhibited malignant progression of ovarian cancer cells. Circ-PGAM1 directly interacted with miR-542-3p, with mutual negative feedback between them. CDC5L was a direct target of miR-542-3p and played an oncogenic role in ovarian cancer cells. Furthermore, the CDC5L protein binds directly to the PEAK1 promoter to promote its transcription. PEAK1 overexpression activated ERK1/2 and JAK2 signaling pathways and promoted malignant biological behaviors of ovarian cancer cells. Circ-PAGM1 silencing combined with miR-542-3p overexpression played the greatest anticancer role in vivo.ConclusionThe circ-PGAM1/miR-542-3p/CDC5L/PEAK1 pathway played an important role in the progression of ovarian cancer and might be a novel therapeutic target for ovarian cancer.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets