Construction and Investigation of circRNA-associated ceRNA Regulatory Network in Molecular Subtypes of Breast Cancer

Abstract

Background: Circular RNAs (circRNAs) act as competing endogenous RNAs (ceRNAs) that indirectly regulate gene expression and function by binding microRNAs (miRNAs). A growing body of evidence indicates that the ceRNA networks can be used as an effective method to investigate cancer; however, the construction and analysis of ceRNA networks, especially circRNA-miRNA-mRNA regulatory network, in different subtypes of breast cancer has not been previously performed. Methods: First, the expression profiles of circRNA, miRNA, and mRNA were downloaded from the GEO database, differentially expressed genes were obtained using GEO2R, and a ceRNA network, was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs, which was consisted of 10 circRNAs, 25 miRNAs and 39 mRNAs. Further studies of BC subtypes based on TCGA datasets were also performed to validate the effect of novel ceRNA network. Results and Discussion: Then, the related genes in the regulatory network were analyzed by GO functional annotation and KEGG pathway enrichment. The analysis showed that targeted genes were enriched in 97 GO terms and 25 KEGG pathways, respectively, involved in the molecular typing of breast cancer. Meanwhile, Kaplan-Meier analysis revealed that three key genes (MKI67, DEF8, and GFRA1) were significantly associated with BC tumor differentiation and prognosis. Conclusion: The current study provides a potential application of ceRNA network within BC subtypes, and may offer new targets for their diagnosis, therapy and prognosis.

Metabolism-regulating non-coding RNAs in breast cancer: roles, mechanisms and clinical applications

“…They play key roles in developmental and pathological processes involving chromatin remodeling, transcription, post-transcriptional modifications and signal transduction [ 12 ]. Breast cancer exhibits a significant number of differentially expressed ncRNAs, some of which are linked to specific subtypes [ 13 – 16 ]. For instance, the differential expression of the miR-99a/let-7c/miR-125b miRNA cluster distinguishes between Luminal A and B subtypes [ 13 ].…”

Development of a circHIPK3-based ceRNA network and identification of mRNA signature in breast cancer patients harboring BRCA mutation

“…It has been shown that the ceRNAs have regulatory roles in post-transcription of cancer cells. Recently, a circRNA-based ceRNA regulatory network has been established to classify breast cancer patients and facilitate the diagnosis, therapy and prognosis ( Zhong et al, 2022 ). In breast cancer, miRNA signature has been developed to predict neoadjuvant chemotherapy responsiveness ( Xing et al, 2021 ).…”

Hsa_circ_0007401 regulates gemcitabine resistance of pancreatic cancer through the hsa-miR-6509-3p/fli1 axis

“…In addition to their potential as biomarkers, circRNAs may also regulate gene expression through their interactions with microRNAs, potentially affecting tumor cell proliferation, migration, invasion, apoptosis, and drug resistance. [12][13][14] In this study, multiple databases were used for the selection of circRNAs, including circbase and cancer-specific circRNA database (CSCD), to ensure rigorous and credible results.…”