Targeting the Vav1/miR‑29b axis as a potential approach for treating selected molecular subtypes of triple‑negative breast cancer

Grassilli,Silvia; Vezzali,Federica; Cairo,Stefano; Brugnoli,Federica; Volinia,Stefano; De Mattei,Monica; Judde,Jean-Gabriel; Bertagnolo,Valeria

doi:10.3892/or.2021.8034

Targeting the Vav1/miR‑29b axis as a potential approach for treating selected molecular subtypes of triple‑negative breast cancer

Authors:
- Silvia Grassilli
- Federica Vezzali
- Stefano Cairo
- Federica Brugnoli
- Stefano Volinia
- Monica De Mattei
- Jean-Gabriel Judde
- Valeria Bertagnolo
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Affiliations: Department of Translational Medicine, University of Ferrara, I-44121 Ferrara, Italy, Xentech, 91000 Evry, France, Department of Medical Sciences, University of Ferrara, I-44121 Ferrara, Italy
Published online on: March 31, 2021 https://doi.org/10.3892/or.2021.8034
Article Number: 83

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Abstract

MicroRNA (miR)‑29b has been reported to play a controversial role in breast cancer, particularly triple‑negative breast cancer (TNBC). Based on our previous data revealing that the PU.1‑mediated expression of miR‑29b in cells from acute myeloid leukemia is sustained by Vav1, the potential role of this multidomain protein in modulating miR‑29b levels in breast tumor cells, in which Vav1 is ecstopically expressed and shows a nuclear accumulation, was investigated. Breast cancer cell lines with various phenotypes and patient‑derived xenograft‑derived TNBC cells were subjected to Vav1 modulation and reverse transcription quantitative PCR of miR‑29b levels. The recruitment of CCAAT enhancer binding protein α (CEBPα) to miR‑29b promoters was investigated by quantitative chromatin immunoprecipitation assays. It was found that Vav1 was essential for the recovery of mature miR‑29b in breast cancer cell lines, and that it promoted the expression of the miRNA in TNBC cells of the mesenchymal molecular subtype by sustaining the transcription of the miR‑29b1/a cluster mediated by CEBPα. The present results suggest that Vav1 is a crucial modulator of miR‑29b expression in breast tumor cells, and this finding may help identify strategies that may be useful in the management of TNBC by targeting the Vav1/miR‑29b axis, as there is a lack of molecular‑based treatments for TNBC.

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