Increased Expression of Circular RNA circ_0005230 Indicates Dismal Prognosis in Breast Cancer and Regulates Cell Proliferation and Invasion via miR-618/ CBX8 Signal Pathway.

Abstract

BACKGROUND/AIMS:

Circular RNAs (circRNAs) are a class of non-coding RNAs. They have been proved to be critically involved in tumorigenesis and progression of malignancies through competing endogenous RNA (ceRNA) mechanism. Nevertheless, the exploration between circRNAs and pathogenesis of breast cancer (BC) is limited. Previously, circ_0005230 was identified upregulated in BC tissues screened by circRNA microarray. In the present study, we aimed to investigate the expression pattern, functional role, and mechanism of circ_0005230 in BC.

METHODS:

qRT-PCR was conducted to elucidate the expression levels of circ_0005230 in BC tissues and cells. Additionally, the clinical severity and prognostic value were investigated. CCK-8, colony-forming, flow cytometric assays were performed. Animal study was conducted to validate the in vitro data. What's more, Transwell assays were induced to detect the cell metastatic properties of circ_0005230 exerts in BC cells. Luciferase reporter assay was used to measure the mechanism of circ_0005230.

RESULTS:

circ_0005230 was overexpressed in BC tissue specimens and cell lines. The overexpression of circ_0005230 was related to adverse phenotypes in the patients with BC. In addition, circ_0005230 could be regarded as a prognostic predictor in BC patients. In vitro and in vivo data demonstrated the cell growth promoting role of circ_0005230. Moreover, circ_0005230 could also promote cell migratory and invasive capacities. For the mechanism investigation, circ_0005230 was proved to be a sponge of miR-618, and expression of miR-618 could regulate CBX8 expression via targeting the 3'UTR of CBX8. Rescue assays also illustrated an oncogenic function of circ_0005230 in BC via acting as a miR-618 sponge to promote CBX8 expression.

CONCLUSION:

circ_0005230/miR-618/CBX8 axis might play a key role in BC tumorigenesis and development.

• Authors: Yi Xu, Yue Yao, Kaiming Leng, Daolin Ji, Lijun Qu, Yueping Liu, Yunfu Cui
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 51 Issue 4 Pg. 1710-1722 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 30504704 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• CBX8 protein, human
• MIRN618 microRNA, human
• MicroRNAs
• RNA, Circular
• RNA
• Polycomb Repressive Complex 1

Topics

• Animals
• Breast Neoplasms (diagnosis, genetics, pathology)
• Carcinogenesis (genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Mice, Nude
• MicroRNAs (genetics)
• Neoplasm Invasiveness (diagnosis, genetics, pathology)
• Polycomb Repressive Complex 1 (genetics)
• Prognosis
• RNA (genetics)
• RNA, Circular
• Up-Regulation