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Article

Platelet-Derived miR-126-3p Directly Targets AKT2 and Exerts Anti-Tumor Effects in Breast Cancer Cells: Further Insights in Platelet-Cancer Interplay

1
Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
2
Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work.
Academic Editor: Silvia S. Barbieri
Int. J. Mol. Sci. 2022, 23(10), 5484; https://doi.org/10.3390/ijms23105484
Received: 22 April 2022 / Revised: 9 May 2022 / Accepted: 12 May 2022 / Published: 13 May 2022
(This article belongs to the Special Issue Molecular Research on Platelet Activity in Health and Disease 2022)
Among the surrounding cells influencing tumor biology, platelets are recognized as novel players as they release microvesicles (MVs) that, once delivered to cancer cells, modulate signaling pathways related to cell growth and dissemination. We have previously shown that physiological delivery of platelet MVs enriched in miR-126 exerted anti-tumor effects in different breast cancer (BC) cell lines. Here, we seek further insight by identifying AKT2 kinase as a novel miR-126-3p direct target, as assessed by bioinformatic analysis and validated by luciferase assay. Both ectopic expression and platelet MV-mediated delivery of miR-126-3p downregulated AKT2 expression, thus suppressing proliferating and invading properties, in either triple negative (BT549 cells) or less aggressive Luminal A (MCF-7 cells) BC subtypes. Accordingly, as shown by bioinformatic analysis, both high miR-126 and low AKT2 levels were associated with favorable long-term prognosis in BC patients. Our results, together with the literature data, indicate that miR-126-3p exerts suppressor activity by specifically targeting components of the PIK3/AKT signaling cascade. Therefore, management of platelet-derived MV production and selective delivery of miR-126-3p to tumor cells may represent a useful tool in multimodal therapeutic approaches in BC patients.
Keywords: breast cancer; microvesicles; miR-126; PIK3/AKT signaling; platelets; polyunsaturated fatty acids breast cancer; microvesicles; miR-126; PIK3/AKT signaling; platelets; polyunsaturated fatty acids
MDPI and ACS Style

Sibilano, M.; Tullio, V.; Adorno, G.; Savini, I.; Gasperi, V.; Catani, M.V. Platelet-Derived miR-126-3p Directly Targets AKT2 and Exerts Anti-Tumor Effects in Breast Cancer Cells: Further Insights in Platelet-Cancer Interplay. Int. J. Mol. Sci. 2022, 23, 5484. https://doi.org/10.3390/ijms23105484

AMA Style

Sibilano M, Tullio V, Adorno G, Savini I, Gasperi V, Catani MV. Platelet-Derived miR-126-3p Directly Targets AKT2 and Exerts Anti-Tumor Effects in Breast Cancer Cells: Further Insights in Platelet-Cancer Interplay. International Journal of Molecular Sciences. 2022; 23(10):5484. https://doi.org/10.3390/ijms23105484

Chicago/Turabian Style

Sibilano, Matteo, Valentina Tullio, Gaspare Adorno, Isabella Savini, Valeria Gasperi, and Maria V. Catani. 2022. "Platelet-Derived miR-126-3p Directly Targets AKT2 and Exerts Anti-Tumor Effects in Breast Cancer Cells: Further Insights in Platelet-Cancer Interplay" International Journal of Molecular Sciences 23, no. 10: 5484. https://doi.org/10.3390/ijms23105484

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