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.

中文翻译：

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CircPGPEP1通过靶向miR-30b促进乳腺癌细胞的生长和转移

背景

环状RNA（circRNA）和微小RNA（miRNA）与肿瘤发生密切相关。乳腺癌是一种具有亚型的异质性疾病。它是女性死亡的主要原因之一，各种 circRNA 和 miRNA 的失调与乳腺癌的发展有关。此外，circPGPEP1(hsa_circ_0050102)可以起到肿瘤促进剂的作用。然而，circPGPEP1 调节乳腺癌信号传导的潜在机制仍不清楚。

客观的

本研究的目的是确定 circPGPEP1 在肿瘤进展过程中的详细作用。使用 RT-qPCR 检查乳腺癌组织和细胞中 circPGPEP1 和 miR-30b 的表达谱。通过蛋白质印迹法测定转染 miR-30b 模拟物的 MCF-7 和 T47D 细胞中 ITGB3 的蛋白水平。此外，使用 CCK8 和 Transwell 检测评估转染乳腺癌细胞的增殖、侵袭和迁移。此外，通过流式细胞术测量了治疗后的癌细胞的凋亡率。使用荧光素酶报告基因测定来探索 miR-30b 和 circPGPEP1/ITGB3 之间的相互作用。

结果

我们的结果显示乳腺癌组织和细胞系中 circPGPEP1 上调，这与患者的不良预后相关。敲除circPGPEP1可抑制癌细胞的增殖、侵袭和迁移，同时促进细胞凋亡。敲低 circPGPEP1 后，miR-30b 的表达增加，但 ITGB3 的水平降低。此外，乳腺癌组织中miR-30b与circPGPEP1和ITGB3呈负相关。此外，miR-30b模拟物抑制乳腺癌细胞的生长，而细胞凋亡则增强。ITGB3 的过度表达可逆转这些效应。此外，miR-30b 模拟物可以消除 oe-circPGPEP1 引起的生物学行为变化。

结论

CircPGPEP1 可以通过靶向 miR-30b 和 ITGB3 作为肿瘤启动子。circPGPEP1/miR-30b/ITGB3轴可能调控乳腺癌细胞的增殖、侵袭、迁移和凋亡，可能成为新的预后和治疗靶点。