A Novel Circular RNA hsa_circRPPH1_015 Exerts an Oncogenic Role in Breast Cancer by Impairing miRNA-326-Mediated ELK1 Inhibition
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...
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Published in | Frontiers in oncology Vol. 10; p. 906 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
24.06.2020
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Emilio Cusanelli, University of Trento, Italy Reviewed by: Longqiang Wang, University of Texas MD Anderson Cancer Center, United States; Olga Brovkina, Federal Medical-Biological Agency, Russia This article was submitted to Cancer Genetics, a section of the journal Frontiers in Oncology |
ISSN: | 2234-943X 2234-943X |
DOI: | 10.3389/fonc.2020.00906 |