Circular RNA PVT1 Promotes Breast Cancer Progression via miR-30b-5p/AEG-1 Axis

Abstract

Abstract Background: Circular RNA PVT1 (circPVT1) has been reported to be a vital modulator in tumorigenesis. However, the detailed regulatory mechanism of circPVT1 in breast cancer (BC) remains largely unclear. Objective: This research is to explore the mechanisms of circPVT1 in breast cancer from different perspectives. Methods: In this work, the expressions of circPVT1 and microRNA-30b-5p (miR-30b-5p) were detected by quantitative real-time PCR (qRT-PCR) in breast cancer tissues and cell lines. The Kaplan-Meierk was adopted to compare disease free survival (DFS) and overall (OS). BC cell lines MDA-MB-231and MCF-7 cell lines were chosen for the following assays. After circPVT1 was depleted, CCK-8 and Transwell assays were performed to examine the cell viability and invasive capacity. Astrocyte elevated gene 1 (AEG-1) protein level was measured by western blot. The competitive endogenous RNA molecular mechanism among circPVT1, miR-30b-5p and AEG-1 was verified by bioinformatics analysis, luciferase-reporter gene assay. Results: In the present study, it was revealed that circPVT1 expression was remarkably evaluated in BC tissues and cell lines than that in the corresponding control group. The Kaplan-Meier analysis shown that high circPVT1 expression had a significantly poorer survival prognosis than those with low circPVT1 expression in DFS (χ2 = 7.174, P = 0.007) and OS (χ2 = 3.946, P = 0.047). CircPVT1 positively regulated the proliferation, migration and invasion progression of BC cells. Besides, miR-30b-5p was identified as a target of circPVT1, and AEG-1 was identified as a target of miR-30b-5p. The depletion of circPVT1 promoted the expression of miR-30b-5p and suppressed AEG-1 expression. Moreover, simultaneous inhibition of miR-30b-5p expression in the circPVT1 knockout group could reverse the inhibition of AEG-1 expression. Conclusion: In conclusion, our results indicate circPVT1 regulates AEG-1 expression by competitively binding to endogenous miR-30b-5p in breast cancer cells. CircPVT1 promoted AEG-1 expression by negatively regulating miR-30b-5p expression to enhance the cell viability, migration, and invasion progression of BC cells. Our results reveal a new molecular therapy target for breast cancer.