Circular RNA S-7 promotes ovarian cancer EMT via sponging miR-641 to up-regulate ZEB1 and MDM2.

Abstract

BACKGROUND:

Ovarian cancer (OC) is one lethal gynecologic cancer, with a 5-year survival rate approximately 47% and localized stage diagnosis of 15%. Circular RNAs are promising biomarkers for malignancies.

METHODS:

CiRS-7 expression was confirmed in 40 paired OC and normal adjacent tissues from 40 OC patients with different TNM stages, lymph node metastasis status and overall survival rate, also 5 different OC cell lines by qRT-PCR. Effects of ciRS-7 silence on OC cell phenotypes were determined in OC cells and Xenograft mouse model. StarBase was used to predict binding sites between ciRS-7 and micRNAs. Pearson correlation analysis and RNA-immunoprecipitation assay were used to determine the association between genes. Point mutation and rescue experiments were applied for molecular mechanism investigation.

RESULTS:

CiRS-7 expression was significantly higher in OC cells and tissues, which was significantly associated with the TNM stages, lymph node metastasis status and overall survival rate in OC patients. CiRS-7 silence inhibited OC cell growth and metastasis. CiRS-7 sponged miR-641 to up-regulate ZEB1 and MDM2 expression in OC development.

CONCLUSION:

CiRS-7 serves as a competing endogenous RNA of miR-641 that promoted cell growth and metastasis in OC, via regulating ZEB1 and MDM2-mediated EMT. High ciRS-7 expression was a poor prognosis of TNM stages, lymph node metastasis status and overall survival rate in OC patients. Targeting ciRS-7/miR-641/ZEB1 or ciRS-7/miR-641/MDM2 axis may be a novel diagnostic, prognostic and therapeutic strategy for OC.

• Authors: Fenghua Zhang, Yun Xu, Wenfeng Ye, Jingting Jiang, Changping Wu
• Journal: Bioscience reports (Biosci Rep) Vol. 40 Issue 7 (07 31 2020) ISSN: 1573-4935 [Electronic] England
• PMID: 32667627 (Publication Type: Journal Article)
• Copyright: © 2020 The Author(s).

Chemical References

• Biomarkers, Tumor
• MIRN641 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• ZEB1 protein, human
• Zinc Finger E-box-Binding Homeobox 1
• long non-coding RNA CDR1AS, human
• MDM2 protein, human
• Proto-Oncogene Proteins c-mdm2

Topics

• Animals
• Biomarkers, Tumor (metabolism)
• Carcinogenesis (genetics)
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lymphatic Metastasis (genetics)
• Male
• Mice
• MicroRNAs (metabolism)
• Neoplasm Staging
• Ovarian Neoplasms (diagnosis, genetics, mortality, surgery)
• Ovariectomy
• Ovary (pathology, surgery)
• Prognosis
• Proto-Oncogene Proteins c-mdm2 (genetics)
• RNA, Long Noncoding (metabolism)
• Survival Rate
• Up-Regulation
• Xenograft Model Antitumor Assays
• Zinc Finger E-box-Binding Homeobox 1 (genetics)