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MiR-3194-3p Inhibits Breast Cancer Progression by Targeting Aquaporin1
Min Wei1,2, Hailang Yu3, Cuixia Cai3
1Clinical Laboratory, Nanshan Maternity and Child Healthcare Hospital, Shenzhen, China.
Abstract:
Increasing evidence indicates that the Aquaporin1 (AQP1) aberrant expression may be related to a wide variety of human cancers, including breast cancer (BC). In the present study, we explore the effects and possible mechanism of miR-3194-3p on the biological behaviors of BC. At first, miR-3194-3p is found to modulate AQP1 expression targeting the 3'-UTR using miRNA target prediction algorithms. MiR-3194-3p expression is markedly downregulated, and AQP1 expression is upregulated in BC tissues compared with adjacent normal breast tissues. Moreover, the differential expression of miR-3194-3p and AQP1 are observed in four BC cells with different malignancy degree. Meanwhile, a significant negative correlation between AQP1 and miR-3194-3p expressions in tumor tissues from 30 BC patients is revealed. miR-3194-3p mimic remarkably inhibits cell proliferation, migration, and invasion as well as promotes apoptosis in MDA-MB-231 cells while miR-3194-3p inhibitors exert an opposite role in MCF-7 cells. Dual-luciferase reporter system demonstrates that AQP1 is a direct target gene of miR-3194-3p. Overexpression of AQP1 by pBABE-puro-AQP1 vector partially abrogates the effect of miR-3194-3p mimic in MDA-MB-231 cells. In short, our results suggest that miR-3194-3p suppresses BC cell proliferation, migration, and invasion by targeting AQP1, providing a novel insight into BC tumorigenesis and treatment.
Insights
MicroRNA-3194-3p suppresses breast cancer (BC) progression by targeting Aquaporin1 (AQP1). This study reveals miR-3194-3p as a potential therapeutic target for BC by inhibiting proliferation and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aberrant Aquaporin1 (AQP1) expression is linked to various human cancers, including breast cancer (BC).
- The role of microRNA-3194-3p (miR-3194-3p) in BC pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the functional role and underlying mechanism of miR-3194-3p in breast cancer biological behaviors.
- To explore the relationship between miR-3194-3p and Aquaporin1 (AQP1) in BC.
Main Methods:
- Bioinformatic prediction of miRNA targets.
- Quantitative real-time PCR to assess gene and miRNA expression in BC tissues and cell lines.
- Cell proliferation, migration, invasion, and apoptosis assays.
- Dual-luciferase reporter assay to validate direct targeting.
- Gene overexpression studies.
Main Results:
- MiR-3194-3p was significantly downregulated, while AQP1 was upregulated in BC tissues and cells.
- MiR-3194-3p mimic inhibited BC cell proliferation, migration, and invasion, and promoted apoptosis.
- AQP1 was identified as a direct target gene of miR-3194-3p.
- AQP1 overexpression partially reversed the inhibitory effects of miR-3194-3p.
Conclusions:
- MiR-3194-3p acts as a tumor suppressor in breast cancer.
- The miR-3194-3p/AQP1 axis plays a crucial role in regulating BC cell proliferation, migration, and invasion.
- Targeting miR-3194-3p offers a potential therapeutic strategy for breast cancer treatment.
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