α4β1整合素调控多发性骨髓瘤(MM)细胞的转运并促进MM疾病的进展。微小RNA(miRNA)既可具有肿瘤抑制因子的作用，又可具有致癌基因的作用，因此它们是肿瘤进化的关键控制因子，并与MM发病的不同阶段有关。我们利用小RNA测序分析展示了α4β1依赖的MM细胞黏附调控了四十种不同miRNA的表达，从而扩展了我们对α4β1参与MM细胞生物学的了解。通过沉默α4整合素亚基，我们验证了在细胞与α4β1配体结合时miR-324-5p和miR-331-3p的特异性上调，并且发现它们的增加水平依赖于Erk1/2和PI3K-Akt信号通路，而不依赖于Src信号通路。在α4β1介导的MM细胞黏附过程中miR-324-5p的表达增强针对Hedgehog(Hh)组分SMO，揭示了miR-324-5p-SMO模块代表了一个α4β1调控的信号通路，可以控制骨髓瘤中Hh依赖的细胞反应。我们的结果为研究α4β1对MM进展的新治疗途径开辟了可能，值得进一步探索。© 2023 The Authors. eJHaem发表于英国血液学协会和John Wiley & Sons有限公司。

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.© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.