Identification of Novel CircRNA-miRNA-mRNA Regulatory Network and Its Prognostic Prediction in Breast Cancer

Abstract

Aim. This study aimed to investigate the expression profiles of circRNAs and candidate circRNA-miRNA-mRNA network in BC. Methods. Differentially expressed circRNAs, miRNAs, and mRNAs (DEcircRNAs, DEmiRNAs, and DEmRNAs) between BC and normal breast tissue samples were screened by analyzing raw data of the RNA sequencing profile. The expression levels of hub genes in 48 pairs of cancerous and tumor-free breast tissues surgically resected from BC patients were determined by RT-qPCR analysis. Results. A total of 145 DEcircRNAs, 140 DEmiRNAs, and 2451 DEmRNAs between BC and normal breast tissue samples were screened out. There were 5 pairs of upcircRNA-downmiRNA-upmRNA network and 20 pairs of downcircRNA-upmiRNA-downmRNA network. EIF4EBP1, DUSP1, EGR2, EZH1, and CBX7 were found to be correlated with overall survival of the patients with BC. The expression level of EIF4EBP1 was increased and the expression levels of DUSP1, EGR2, EZH1, and CBX7 were decreased in cancerous breast tissues compared to tumor-free breast tissues p < 0.0001 . The RT-qPCR results from 48 BC patients were consistent with the bioinformatics results. Conclusion. This study provides a novel perspective to study circRNA-miRNA-mRNA network in BC and assists in the identification of new potential biomarkers to be used for diagnostic and prognostic purposes.

Has_circ_0000069 expression in breast cancer and its influences on prognosis and cellular activities

“…For instance, has_circ_102229 was upregulated in triple-negative breast cancer tissues and associated with poor prognosis, as well as could facilitate tumor progression by regulating miR-152-3p/PFTK1 pathway [25]. A recent study identified circRNA-miRNA-mRNA network and prognostic prediction in breast cancer, in which has_circ_0000069 was an upregulated circRNA [20]. Consistent with the expression pattern, has_circ_0000069 expression was upregulated in breast cancer tissues in this study.…”

“…Has_circ_0000069 is aberrantly expressed in several cancers, such as cervical cancer [17], pancreatic cancer [18], and colorectal cancer [19]. A recent RNA sequencing profile study identified many circRNA-miRNA-mRNA networks, including has_circ_0000069 [20].…”

Current evidence on circRNAs as potential theranostic markers for detecting chemoresistance in breast cancer: a systematic review and meta‑analysis

“…Many studies have also confirmed that several specific circRNAs are consistently expressed in human tissues and blood. Therefore, circRNAs have the chance to be excellent biomarkers for BC diagnosis, prognosis and drug resistance assessment 3 , 33 , 48 , 49 .…”

“…Many studies have also confirmed that several specific circRNAs are consistently expressed in human tissues and blood. Therefore, circRNAs have the chance to be excellent biomarkers for BC diagnosis, prognosis and drug resistance assessment 3,33,48,49 . Some studies have concentrated on the effects of circRNAs on chemoresistance in breast, cervical 50 , colorectal 51,52 , gastric 53,54 , lung 55 , oral 56 , ovarian 57 , pancreatic 58 and prostate 59 cancers.…”

“…Several studies found that the expression of certain circRNAs was associated with increased drug resistance and a poor prognosis in BC patients 10 , 22 , 23 , 32 . Preclinical and clinical observational studies have shown that circRNA expression profiles can help identify patients at possible high risk for chemotherapy-resistant BC 11 , 33 . Therefore, we attempted to conduct a comprehensive systematic review and meta-analysis of published studies on circRNA-mediated chemoresistance in BC.…”