多发性骨髓瘤骨髓间质中的氧化应激对疾病进展和药物耐药性产生影响。最近的研究发现，Hippo信号通路与miRNA生物合成和实体肿瘤中的氧化应激相关。氧化应激与miRNA通路在几种癌症中相互影响。我们的研究小组最近发现TAZ在多发性骨髓瘤中具有抑制肿瘤的功能。然而，TAZ在多发性骨髓瘤中的氧化应激作用尚不明确。我们旨在研究TAZ在髓瘤细胞对骨髓氧化应激的响应中的作用。我们假设TAZ可能与多发性骨髓瘤中的氧化应激表型和独特的miRNA特征相关。通过使用人类骨髓瘤细胞系和临床样本，我们证明TAZ促进了骨髓瘤细胞对氧化应激和抗癌治疗诱导的细胞毒作用的敏感性，通过诱导miR-224抑制MM中的NRF2抗氧化计划。我们显示在MM中低表达的TAZ蛋白会赋予细胞对氧化应激的抗性表型。此外，我们提供证据表明，在表达低量TAZ蛋白的骨髓瘤细胞中过表达miR-224可抑制细胞生长并增强对抗骨髓瘤治疗的敏感性。我们的研究结果揭示了TAZ在多发性骨髓瘤中对氧化应激反应的潜在作用，其机制是通过miR-224-NRF2分子通路实现的。这为探索miR-224作为潜在的分子靶点以调节TAZ表达并增强骨髓瘤对治疗的敏感性提供了科学基础。©2023年作者。由Wiley Periodicals LLC出版的《癌症报告》发表。

Oxidative stress within the bone marrow niche of multiple myeloma contributes to disease progression and drug resistance. Recent studies have associated the Hippo pathway with miRNA biogenesis and oxidative stress in solid tumors. Oxidative stress and miRNA pathway inter-relates in several cancers. Our group recently showed that TAZ functions as a tumor suppressor in MM. However, the role of TAZ in oxidative stress in MM is unknown.We sought to examine the role of TAZ in myeloma cells' response to BM oxidative stress. We postulated that TAZ might be associated with an oxidative stress phenotype and distinct miRNA signature in MM.Using human myeloma cell lines and clinical samples, we demonstrate that TAZ promotes myeloma cells' sensitivity to oxidative stress and anticancer-induced cytotoxicity by inducing miR-224 to repress the NRF2 antioxidant program in MM. We show that low expression of TAZ protein confers an oxidative stress-resistant phenotype in MM. Furthermore, we provide evidence that overexpression of miR-224 in myeloma cells expressing low amounts of TAZ protein inhibits cell growth and enhances sensitivity to anti-myeloma therapeutics.Our findings uncover a potential role for TAZ in oxidative stress response in MM via the miR-224-NRF2 molecular pathway. This provides the scientific ground to explore miR-224 as a potential molecular target to modify TAZ expression and enhance myeloma sensitivity to treatment.© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.