Regulation of miRNA expression by α4β1 integrin-dependent multiple myeloma cell adhesion.

Autor: Rodríguez-García Y; Department of Molecular Biomedicine Centro de Investigaciones Biológicas Margarita Salas (CSIC) Madrid Spain., Martínez-Moreno M; Department of Molecular Biomedicine Centro de Investigaciones Biológicas Margarita Salas (CSIC) Madrid Spain., Alonso L; Genetic and Molecular Epidemiology Group Spanish National Cancer Research Centre and CIBERONC Madrid Spain., Sánchez-Vencells A; Department of Molecular Biomedicine Centro de Investigaciones Biológicas Margarita Salas (CSIC) Madrid Spain., Arranz A; Department of Molecular Biomedicine Centro de Investigaciones Biológicas Margarita Salas (CSIC) Madrid Spain., Dagà-Millán R; Department of Molecular Biomedicine Centro de Investigaciones Biológicas Margarita Salas (CSIC) Madrid Spain., Sevilla-Movilla S; Department of Molecular Biomedicine Centro de Investigaciones Biológicas Margarita Salas (CSIC) Madrid Spain., Valeri A; Department of Translational Hematology CNIO-ISCIII, CIBERONC Hospital Universitario 12 de Octubre, imas12 Universidad Complutense Madrid Spain., Martínez-López J; Department of Translational Hematology CNIO-ISCIII, CIBERONC Hospital Universitario 12 de Octubre, imas12 Universidad Complutense Madrid Spain., Teixidó J; Department of Molecular Biomedicine Centro de Investigaciones Biológicas Margarita Salas (CSIC) Madrid Spain.
Jazyk: angličtina
Zdroj: EJHaem [EJHaem] 2023 Jul 25; Vol. 4 (3), pp. 631-638. Date of Electronic Publication: 2023 Jul 25 (Print Publication: 2023).
DOI: 10.1002/jha2.756
Abstrakt: The α4β1 integrin regulates the trafficking of multiple myeloma (MM) cells and contributes to MM disease progression. MicroRNAs (miRNAs) can have both tumor suppressor and oncogenic roles and thus are key controllers of tumor evolution, and have been associated with different phases of MM pathogenesis. Using small RNAseq analysis, we show here that α4β1-dependent MM cell adhesion regulates the expression of forty different miRNAs, therefore expanding our current view of the α4β1 involvement in MM cell biology. Specific upregulation of miR-324-5p and miR-331-3p in cells attached to α4β1 ligands was confirmed upon silencing the α4 integrin subunit, and their increased levels found to be dependent on Erk1/2- and PI3K-Akt-, but not Src-dependent signaling. Enhanced miR-324-5p expression upon α4β1-mediated MM cell adhesion aimed the hedgehog (Hh) component SMO , revealing that the miR-324-5p- SMO module represents a α4β1-regulated pathway that could control Hh-dependent cellular responses in myeloma. Our results open new therapy research avenues around the α4β1 contribution to MM progression that deserve to be investigated.
Competing Interests: The authors declare no financial interests.
(© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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