CircRNA RPPH1 Facilitates the Aggravation of Breast Cancer Development by Regulating miR-542-3p/ARHGAP1 Pathway.

Abstract

Background: Circular RNAs (circRNAs) have important roles in human malignancies, including breast cancer (BC). In this study, we explored the function of circRNA ribonuclease P RNA component H1 (circ_RPPH1) in BC development and clarify the mechanistic pathway. Materials and Methods: Expression of circ_RPPH1, microRNA-542-3p (miR-542-3p), and Rho GTPase-activating protein 1 (ARHGAP1) in BC tissues and cells was determined by quantitative real-time polymerase chain reaction or Western blot assay. The stability of circ_RPPH1 was confirmed by RNase R and actinomycin D treatment. Cell viability and colony formation ability were measured by methyl thiazolyl tetrazolium (MTT) assay and colony formation assay, respectively. Western blot analysis was also used to detect proliferation biomarker (Ki67) and epithelial-mesenchymal transition (EMT) biomarkers (E-cadherin, N-cadherin, and vimentin). Flow cytometry and Transwell assays were performed to monitor cell apoptosis, migration, and invasion. The binding potency between miR-542-3p and circ_RPPH1 or ARHGAP1 was validated by dual-luciferase reporter assay. Functional role of circ_RPPH1 in vivo was investigated by xenograft tumor reporter assay. Results: Upregulation of circ_RPPH1 and ARHGAP1, and downregulation of miR-542-3p were detected in BC tissues and cells. circ_RPPH1 knockdown or miR-542-3p introduction inhibited BC cell proliferation and metastasis, while promoted apoptosis in vitro. circ_RPPH1 sponged miR-542-3p to upregulate ARHGAP1 expression, thereby affecting BC progression. Moreover, depletion of circ_RPPH1 suppressed tumor growth in vivo. Conclusions: circ_RPPH1 contributed to BC tumorigenesis by sponging miR-542-3p and upregulating ARHGAP1, affording a novel mechanistic pathway in BC development.