MiR-466 as a poor prognostic predictor suppresses cell proliferation and EMT in breast cancer cells by targeting PSMA7

Y. Xiao, S.-J. Zhang, X. Yan, C. Wu, Q.-W. Liu, H.-X. Dong, L.-J. Wang, Y. Hu

Senior Department of Oncology, the Fifth Medical Center of PLA General Hospital, Beijing, China. hu_yi2018@126.com

 

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• Oncology

OBJECTIVE: MiR-466 has been reported to exert a tumor-suppressive role in several cancers, including colorectal cancer and osteosarcoma, but its clinical significance and functional mechanisms in breast cancer (BC) pathogenesis still remain elusive.

PATIENTS AND METHODS: The expression of miR-466 was determined using reverse transcription quantitative PCR. The clinical significance of miR-466 in BC patients was assessed by Chi-square test, Kaplan-Meier method and Cox regression analyses. Functional experiments, including CCK-8 and transwell assays, were performed to analyze cell proliferation, migration and invasion ability. The association between miR-466 and proteasome subunit α7 (PSMA7) was confirmed by Luciferase reporter assay.

RESULTS: Here, we first observed that the expression of miR-466 was significantly downregulated in BC tissues and cell lines. The decreased miR-466 expression was significantly associated with tumor size (p = 0.003), lymph node metastasis (p = 0.008), TNM stage (p = 0.032) and poor survival rate. In addition, miR-466 was identified as an independent prognostic factor for BC patients. We further found that the overexpression of miR-466 significantly inhibited cell proliferation, migration and invasion. Mechanistically, PSMA7 was a potential target gene of miR-466 and negatively regulated miR-466 in BC cells. Oncomine database and Kaplan-Meier overall survival analysis indicated that upregulation of PSMA7 was associated with poor prognosis of BC patients. The rescue experiments demonstrated that PSMA7 overexpression reversed the effects of miR-466 on cell proliferation, migration, invasion and EMT transcription factors (E-cadherin, N-cadherin, and vimentin).

CONCLUSIONS: Collectively, these results suggest that the miR-466/PSMA7 axis might have potential as a therapeutic target for BC treatment.

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