Image_3_A Novel Circular RNA hsa_circRPPH1_015 Exerts an Oncogenic Role in Breast Cancer by Impairing miRNA-326-Mediated ELK1 Inhibition.JPEG

Background: Breast cancer (BC) represents a heterogeneous disease with distinct subtypes and high tumor metastatic potentials. Recent researchers identify the implication of circular RNAs (circRNAs) in the initiation of BC. Herein, we uncover a novel circRNA hsa_circRPPH1_015 as a tumor promoter in BC.

Methods: A total of 86 paired cancerous and non-cancerous tissues were surgically resected and collected from BC patients. Cell proliferation, colony formation, and cell invasion were examined by Edu staining, clone formation assays, propidium iodide (PI)-labeled flow cytometry, and Transwell invasion assays. PCNA, Ki67, MMP-2, MMP-9, Cyclin D1, and CDK4 expression was assayed using Western blot analysis. RNA pull-down, dual-luciferase reporter gene assay, and RNA binding protein immunoprecipitation (RIP) assay were performed to investigate the relationships among hsa_circRPPH1_015, microRNA-326 (miR-326), and ELK1. The tumor growth of human BC MCF-7 cells in vivo was evaluated in nude mice by subcutaneous xenografts of MCF-7 cells.

Results: hsa_circRPPH1_015 expression was upregulated in BC tissues. Knockdown of hsa_circRPPH1_015 restrained the aggressive behavior of MCF-7. hsa_circRPPH1_015 could bind to miRNA-326 that negatively regulates ELK1. Elevation of miRNA-326 expression resulted in inhibition of cell proliferation, colony formation, and cell invasion of MCF-7. Disturbance of miRNA-326 or overexpression of ELK1 restored the proliferation and aggressiveness in hsa_circRPPH1_015-depleted MCF-7 cells. Tumor growth of MCF-7 cells in vivo was reduced in nude mice lack of endogenous hsa_circRPPH1_015 expression.

Conclusion: Overall, the present study demonstrates that hsa_circRPPH1_015 was an oncogene and unfavorable prognostic factor in BC, providing an exquisite therapeutic target for BC.