Abstract

Purpose Circular RNA as a competitive endogenous RNA (ceRNA) plays a significant role in the pathogenesis and progression of breast cancer. In this study, a circular RNA-related ceRNA regulatory network was constructed, which provides new biomarkers and therapeutic targets for the treatment of breast cancer. Materials and methods. The expression profile datasets (GSE101123, GSE143564, GSE50428) of circRNAs, miRNAs, and mRNAs were downloaded from the GEO database, and then differentially expressed RNAs (DEcircRNAs, DEmiRNAs, DEmRNAs) were obtained through the CSCD, TargetScan, miRDB, and miRTarBase databases. CircRNA-miRNA pairs and miRNA-mRNA pairs were constructed. Finally, a ceRNA regulatory network was established. Downstream analysis of the ceRNA network included GO, KEGG analysis, survival analysis, sub-network construction, the BCIP, and qRT-PCR verification. Results In total, 144 differentially expressed (DE) DEcircRNA, 221 DEmiRNA, and 1211 DEmRNA were obtained, and 96 circRNA-miRNA pairs and 139 miRNA-mRNA pairs were constructed by prediction. The ceRNA regulatory network (circRNA-miRNA-mRNA) was constructed, which included 42 circRNA, 36miRNA, and 78 mRNA. GO function annotation showed genes were mainly enriched in receptor activity activated by transforming growth factor beta (TGF-beta) and in the regulation of epithelial cell apoptosis. KEGG analysis showed genes were mainly enriched in the TGF-beta signaling, PI3K-Akt signaling, and Wnt signaling pathways. Four genes associated with survival and prognosis of breast cancer were obtained by survival analysis, the prognostic sub-network included 4 circRNA, 4 miRNA, and 4 mRNA. BCIP analysis and qRT-PCR verification confirmed that relative mRNA expression levels were consistent with those in the GEO database. Conclusion A circRNA-related ceRNA regulatory network was constructed for breast cancer in this study and key genes affecting pathogenesis and progression were identified. These findings may help better understand and further explore the molecular mechanisms that affect the progression and pathogenesis of breast cancer.

Highlights

  • Breast cancer is the most common malignancy and poses a serious threat to the health of women worldwide

  • Through the analysis of breast cancer data in the Breast Cancer Integrated Platform (BCIP), the results show that the expression value of the four mRNAs in adjacent normal tissues (AdjN) and breast cancer were consistent with the Gene Expression Omnibus (GEO) database (Figure 9)

  • Breast cancer datasets from the GEO database were analyzed and the findings formed the basis for the construction of a circRNA-related competitive endogenous RNA (ceRNA) regulatory network for breast cancer

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Summary

Introduction

Breast cancer is the most common malignancy and poses a serious threat to the health of women worldwide. In 2020, new cases of breast cancer worldwide accounted for 30% of all malignant tumors, and it is the second leading cause of cancer-related deaths among women [1]. Despite the continuous development of medical technology and the decline in mortality rates, the incidence of breast cancer is still increasing worldwide [2]. Breast cancer is a systemic disease, and its treatment methods include surgery, chemotherapy, targeted therapy, radiotherapy, immunotherapy, and neoadjuvant therapy. There are various treatment methods, the mortality rate of breast cancer remains high due to the high recurrence rate, distant metastasis, and drug resistance. There is an urgent need for new biomarkers and therapeutic targets for breast cancer

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