Scholarlink

<p>We investigated the clinical and functional role of the miR-106a-363 cluster in adult acute myeloid leukemia (AML). LAML miRNA-Seq TCGA analyses revealed that high expression of miR-106a-363 cluster members was associated with inferior survival, and miR-106a-5p and miR-20b-5p levels were significantly elevated in patients with adverse risk AML. Overexpression of the miR-106a-363 cluster and its individual members in a murine AML model significantly accelerated leukemogenesis. Proteomics analysis of leukemic bone marrow cells from these models emphasized the deregulation of proteins involved in intracellular transport, protein complex organization and mitochondrial function, driven predominantly by miR-106a-5p. These molecular alterations suggested mitochondrial activation as a potential mechanism for the observed increase in leukemogenicity. High-resolution respirometry and STED microscopy confirmed that miR-106a-5p enhances mitochondrial respiratory activity and increases mitochondrial volume. These findings demonstrate that the miR-106a-363 cluster, and particularly miR-106a-5p, contribute to AML progression through modulation of mitochondrial function and deregulation of mitochondria-coordinated pathways.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The proto-oncogenic miR-106a-363 cluster enhances adverse risk acute myeloid leukemia through mitochondrial activation

  • 期刊论文

  • 发表日期：

    2025年3月17日

查看全文
  • Nadine Sperb,
  • Irina A. Maksakova,
  • Leo Escano,
  • Libin Abraham,
  • Liam MacPhee,
  • Ariene Cabantog,
  • Dexter Kim,
  • Mansen Yu,
  • Kathrin Krowiorz,
  • Junbum Im,
  • Sarah Grasedieck,
  • Nicole Pochert,
  • Christoph Ruess,
  • Reinhild Rösler,
  • Stephane Flibotte,
  • Tobias Maetzig,
  • Enrico Calzia,
  • Lars Palmqvist,
  • Sebastian Wiese,
  • Linda Fogelstrand,
  • Michael R. Gold,
  • Arefeh Rouhi,
  • Florian Kuchenbauer

摘要

We investigated the clinical and functional role of the miR-106a-363 cluster in adult acute myeloid leukemia (AML). LAML miRNA-Seq TCGA analyses revealed that high expression of miR-106a-363 cluster members was associated with inferior survival, and miR-106a-5p and miR-20b-5p levels were significantly elevated in patients with adverse risk AML. Overexpression of the miR-106a-363 cluster and its individual members in a murine AML model significantly accelerated leukemogenesis. Proteomics analysis of leukemic bone marrow cells from these models emphasized the deregulation of proteins involved in intracellular transport, protein complex organization and mitochondrial function, driven predominantly by miR-106a-5p. These molecular alterations suggested mitochondrial activation as a potential mechanism for the observed increase in leukemogenicity. High-resolution respirometry and STED microscopy confirmed that miR-106a-5p enhances mitochondrial respiratory activity and increases mitochondrial volume. These findings demonstrate that the miR-106a-363 cluster, and particularly miR-106a-5p, contribute to AML progression through modulation of mitochondrial function and deregulation of mitochondria-coordinated pathways.