Abstract
Background
Circular RNAs (circRNAs) and microRNAs (miRNAs) are closely associated with tumorigenesis. Breast cancer is a heterogeneous disease with subtypes. It is one of the leading causes of death in women, and dysregulation of various circRNAs and miRNAs are involved in the development of breast cancer. Furthermore, circPGPEP1(hsa_circ_0050102) could function as a tumor promoter. However, the potential mechanisms of circPGPEP1-modulated signaling in breast cancer are still unknown.
Objective
The aim of this study was to identify the detailed roles of circPGPEP1 during tumor progression. The expression profiles of circPGPEP1 and miR-30b in breast cancer tissues and cells were examined using RT-qPCR. The protein levels of ITGB3 in MCF-7 and T47D cells transfected with miR-30b mimics were determined by western blotting. Additionally, the proliferation, invasion and migration of transfected breast cancer cells were evaluated using CCK8 and Transwell assays. Moreover, the apoptotic rates of treated cancer cells were measured by flow cytometry. Luciferase reporter assay was used to explore the interaction between miR-30b and circPGPEP1/ITGB3.
Results
Our results revealed upregulation of circPGPEP1 in breast cancer tissues and cell lines, which was associated with poor prognosis in the patients. Knockdown of circPGPEP1 inhibited the proliferation, invasion and migration of cancer cells, while cell apoptosis was promoted. The expression of miR-30b was increased but the levels of ITGB3 were decreased following the knockdown of circPGPEP1. Furthermore, miR-30b was negatively correlated with circPGPEP1 and ITGB3 in breast cancer tissues. In addition, miR-30b mimics suppressed the growth of breast cancer cells, whereas cell apoptosis was enhanced. These effects were reversed by the overexpression of ITGB3. Furthermore, miR-30b mimics could abrogate the biological behavior changes caused by oe-circPGPEP1.
Conclusion
CircPGPEP1 could function as a tumor promoter by targeting miR-30b and ITGB3. The circPGPEP1/miR-30b/ITGB3 axis may regulate the proliferation, invasion, migration and apoptosis of breast cancer cells, which could be novel prognostic and therapeutic target.
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Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request.
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The authors express their sincere thanks to the seniors and colleagues for providing adequate guidance, scientific and technical discussions and necessary support for this research article. The first author and the co-author acclaim the reviewers and editor for their valuable comments and suggestions.
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Both authors designed the study and carried out the experiments. They both analyzed the data and drafted the manuscript.
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Yongjia Tan declares that she has no conflict of interest. Xiang Wang declares that he has no conflict of interest.
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Tan, Y., Wang, X. CircPGPEP1 promotes the growth and metastasis of breast cancer cells by targeting miR-30b. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00376-9
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DOI: https://doi.org/10.1007/s13273-023-00376-9