Hsa_circ_0005273 acts as a sponge of miR-509-3p to promote the malignant behaviors of breast cancer by regulating HMMR expression

Abstract

Background: Breast cancer (BC) is a common malignant tumor that threatens the health of women worldwide. Hsa_circ_0005273 has been identified as a carcinogenic factor in some solid tumors, including BC. However, the molecular mechanism of circ_0005273 in BC is poorly defined.

Methods: The expression of circ_0005273, miR-509-3p, and hyaluronan-mediated motility receptor (HMMR) mRNA in BC was detected by quantitative real-time polymerase chain reaction. Cell proliferation, migration, invasion, and apoptosis were detected by 5-ethynyl-2'-deoxyuridine, transwell, and flow cytometry assays. The glycolysis level was detected via specific kits. Western blot was used to detect protein expression. Binding between miR-509-3p and circ_0005273 or HMMR was also verified by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays. Xenograft tumor model was used to detect tumor changes in mice, and immunohistochemistry assay was employed to detect Ki-67 abundance.

Results: Circ_0005273 was increased in BC tissues and cells. Circ_0005273 knockdown might inhibit BC cell proliferation, migration, invasion, glutamine metabolism, and induce apoptosis. Circ_0005273 was a miR-509-3p, and the repression role of circ_0005273 absence on BC cell development was weakened by miR-509-3p inhibitor or HMMR overexpression. Circ_0005273 up-regulated the expression of HMMR by sponging miR-509-3p. Additionally, circ_0005273 silencing might hinder tumor growth in vivo.

Conclusion: Circ_0005273 knockdown might repress BC cell malignant behaviors by regulating the miR-509-3p/HMMR axis, which might provide a potential therapeutic target for BC.

Keywords: BC; HMMR; circ_0005273; miR-509-3p; proliferation.