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

Abstract

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.

A novel circular RNA circPPFIA1 promotes laryngeal squamous cell carcinoma progression through sponging miR-340-3p and regulating ELK1 expression

“…We demonstrated that ELK1 is upregulated in LSCC and acts as a target gene of miR-340-3p as well as a ceRNA of circPPFIA1. ELK1 has been reported to be targeted by miR-30-5p, miR-185-5p, and miR-326 [32][33][34], but this is the first study wherein ELK1 was proven to be a target of miR-340-3p. However, we did not determine the downstream genes activated by ELK1.…”

CircRPPH1 promotes the stemness of gastric cancer cells by targeting miR‐375/SLC7A11 axis

“…Previous literature has manifested that circRNAs are also correlated with CSC progression; however, the roles of circRPPH1 in GC progression has never been revealed before. Currently, we found that progression, [17][18][19][31][32][33] among which, YAP1, miR-296-5p, and HMGA2…”

“…16 As a result, the relationship between circRNAs and miR-375 in GC stemness attracted our interests. Recently, circRPPH1 was firstly identified in breast cancer 17 and found to hold oncogenic roles in breast cancer progression. 18 Furthermore, it was found that circRPPH1 could promote the cell proliferation, migration and invasion of non-small cell lung cancer.…”

Circular RNAs Interaction with MiRNAs: Emerging Roles in Breast Cancer

“…There is evidence that cancer stem cells (CSCs) are the initiator cells of cancers and are responsible for cancer treatment failure owing to their pluripotency and self-renewal characteristics, leading to tumor recurrence [102,103]. Other circRNAs also mediate breast cancer cell development and progression, including hsa_circ_001783, hsa_circRNA _002178, hsa_circRPPH1_015, circ_0007255, circ-TFF1, hsa_circ_0000515, and hsa_circ_0068033, via sponging miR-200c-3p, miR-328-3p, miR-326, miR-335-5p, miR-326, miR-296-5p, and miR-659, respectively [104][105][106][107][108][109][110].…”