Abstract

Background: Circular RNAs (circRNAs) have been shown to play important roles in the development and progression of human cancers. Emerging evidence shows that circRNAs have the potential to be promising biomarkers for cancer diagnosis and prognosis. However, the roles of circRNAs in breast cancer axillary lymph node metastasis (ALNM) remain to be determined. Methods: Transcriptome sequencing was utilized to screen the differentially expressed circRNAs in three breast cancer tissues with ALNM and three without ALNM. Differentially expressed circRNAs were further verified by quantitative real-time PCR. Moreover, receiver operating characteristic (ROC) curve analysis was performed to calculate the value of circRNAs to distinguish breast cancer tissues with ALNM and those without ALNM. To explore the potential mechanism of the circRNAs, a circRNA–miRNA–mRNA network was constructed based on the CircInteractome, circBank, and mirDIP online software. Results: In total, 31 differentially expressed circRNAs were identified by transcriptome sequencing; among them, 21 were upregulated and 10 were downregulated in breast cancer with ALNM compared to those without ALNM. Circ_0000160 was validated to be downregulated in breast cancer tissues with ALNM compared with those without ALNM. The ROC curve showed the ability of circ_0000160 to distinguish breast cancer tissues with ALNM and those without ALNM, with an area under the curve of 0.7435. Furthermore, bioinformatics analysis revealed that the predicted mRNAs for circ_0000160 may be related to lymph node metastasis. The predicted mRNAs for circ_0000160 may be involved in many cancer-related pathways. Conclusion: A decreased expression of circ_0000160 was found in breast cancer with axillary lymph node metastasis. Circ_0000160 may have the potential to distinguish breast cancer with axillary lymph node metastasis from those without axillary lymph node metastasis.

Highlights

  • Breast cancer is one of the most common malignant tumors and the leading cause of cancer-related death in women

  • We investigated the profile of circRNAs using transcriptome sequencing and quantitative real-time PCR in breast cancer tissues with and without Axillary lymph node metastasis (ALNM)

  • To identify dysregulated circRNAs associated with breast cancer ALNM, transcriptome sequencing was performed on three breast cancer tissues with ALNM and three without ALNM (Figure 1A)

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Summary

Introduction

Breast cancer is one of the most common malignant tumors and the leading cause of cancer-related death in women. Deaths are usually caused not by the primary tumor but by metastases (Wang et al, 2020; Kim, 2021). Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules and are the downstream products of precursor mRNA back-splicing (Vo et al, 2019). Their high abundance, stability, evolutionary conservation among species, and high cell and tissue specificity endow circRNAs with the potential as molecular biomarkers for cancer diagnosis (Wang S. et al, 2021; Wei et al, 2021). The roles of circRNAs in breast cancer axillary lymph node metastasis (ALNM) remain to be determined

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