CircUBE2D2 regulates HMGB1 through miR-885-5p to promote ovarian cancer malignancy

Abstract

Background

The newly discovered CircUBE2D2 has been shown to abnormally upregulate and promote cancer progression in a variety of cancers. The present study explored circUBE2D2 (hsa_circ_0005728) in Ovarian Cancer (OC) progression.

Methods

CircUBE2D2, miR-885-5p, and HMGB1 were examined by RT-qPCR or WB. SKOV-3 cell functions (including cell viability, apoptosis, migration, and invasion) were validated using the CCK-8, flow cytometry, scratch assay, and transwell assay, respectively. The direct relationship between miR-885-5p and circUBE2D2 or HMGB1 was confirmed by a dual-luciferase reporter and RNA pull-down analysis. circUBE2D2′s role in vivo tumor xenograft experiment was further probed.

Results

OC tissue and cell lines had higher circUBE2D2 and HMGB1 and lower miR-885-5p. Mechanically, CircUBE2D2 shared a binding relation with miR-885-5p, while miR-885-5p can directly target HMGB1. Eliminating circUBE2D2 or miR-885-5p induction inhibited OC cell activities. However, these functions were relieved by down-regulating miR-885-5p or HMGB1 induction. Furthermore, circUBE2D2 knockout reduced tumor growth.

Conclusion

CircUBE2D2 regulates the expression of HMGB1 by acting as a sponge of ceRNA as miR-885-5p, thereby promoting the control of OC cell proliferation and migration and inhibiting cell apoptosis. Targeting CircUBE2D2 could serve as a new potential treatment strategy for OC.

Keywords
Ovarian Cancer; CircUBE2D2; miR-885-5p; ceRNA; HMGB1

Highlights

• CircUBE2D2 subcellular localization and RNAse R resistance analysis.

• Expression patterns of circUBE2D2 and miR-885-5p.

• CircUBE2D2 silencing inhibits SKOV-3 cell malignant phenotypes.

• CircUBE2D2 serves as the ceRNA of miR-885-5p.