{
  "abstract": "Background: Acute myeloid leukemia (AML) is a hematological malignancy characterized by impaired differentiation of hematopoietic progenitor cells, leading to the disruption of normal hematopoiesis. Despite significant therapeutic advances, important gaps remain in the understanding of AML biology, limiting the development of effective targeted therapies. Dynamic remodeling of the actin cytoskeleton is essential for multiple cellular processes, including proliferation, migration, and adhesion, many of which are dysregulated in AML. RHOA and RHOC are closely related Rho GTPases well established as regulators of actin dynamics. However, their specific roles and the molecular mechanisms that distinguish their functions remain largely unknown. Aim: To investigate the roles of RHOA and RHOC in regulating actin cytoskeleton dynamics in AML cells by evaluating actin polymerization and key proteins involved in actin remodeling. Methods: OCI-AML3 and U937 cells with stable knockdown or overexpression of RHOA or RHOC generated by lentiviral transduction were used. Actin polymerization was assessed by flow cytometry following phalloidin staining. The expression of FMNL1, mDia, profilin, RAC1, total RAC, phosphorylated cofilin, total cofilin and Arp3 was evaluated by western blot. Profilin subcellular localization was analyzed by fluorescence microscopy. Results: In OCI-AML3 cells, RHOC knockdown increased actin polymerization, whereas RHOA knockdown showed variable effects. The overexpression of either RHOA or RHOC also increased F-actin levels. Conversely, in U937 cells, RHOA knockdown significantly reduced actin polymerization, while RHOC knockdown showed a similar trend, indicating cell context-dependent effects. Mechanistic analyses showed that RHOC knockdown in OCI-AML3 cells increased the expression of RAC1 and total RAC, FMNL1, mDia and phospho-cofilin, whereas RHOA knockdown increased mDia levels. Both RHOA and RHOC overexpression increased mDia expression in OCI-AML3 cells, while FMNL1 was selectively upregulated by RHOC overexpression. In U937 cells, RHOA knockdown reduced FMNL1, mDia, profilin and Arp3, whereas RHOC knockdown decreased mDia expression levels. Given that profilin function depends on its subcellular localization, we next evaluated its intracellular distribution. RHOC overexpression promoted a redistribution of profilin from a predominantly nuclear localization to both nuclear and cytoplasmic compartments in OCI-AML3 cells, suggesting a role for RHOC in regulating profilin dynamics. Discussion and conclusions: Our findings demonstrate that RHOA and RHOC exert non-redundant and context-dependent functions in the regulation of actin cytoskeleton remodeling in AML. These GTPases differentially modulate the RAC/cofilin, FMNL1/mDia and Arp2/3 pathways, while RHOC also regulates profilin intracellular localization, identifying a previously unrecognized component of RHOC signaling. Together, these findings provide new mechanistic insights into actin regulation in AML and identify distinct RHOA, and RHOC, dependent pathways as potential therapeutic vulnerabilities.",
  "abstract_shown": true,
  "affiliations": [
    "Universidade Federal de São Paulo, São Paulo, SP, Brazil",
    "Universidade Estadual de Campinas, Campinas, SP, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sofia Santos MOSNA"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Carolina Clares RAMALHO"
    },
    {
      "affs": [
        1
      ],
      "name": "Adriana da Silva Santos DUARTE"
    },
    {
      "affs": [
        1
      ],
      "name": "Sara Teresinha Olalla SAAD"
    },
    {
      "affs": [
        0
      ],
      "name": "Mariana LAZARINI"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/em9p72p1z66vg.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.107582",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926013295",
  "id": "em9p72p1z66vg",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.107582",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "1312|Protein Kinase Regulation and GTPase Signaling"
    ]
  ],
  "openalex": "W7223563919",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/em9p72p1z66vg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:38Z",
      "native_id": "fc382c4a94d54fe8a434cab5dcb6fe65",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.107582"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Kinase Regulation and GTPase Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "DISTINCT ROLES OF RHOA AND RHOC IN ACTIN CYTOSKELETON DYNAMICS IN MYELOID CELLS",
  "title_text": "DISTINCT ROLES OF RHOA AND RHOC IN ACTIN CYTOSKELETON DYNAMICS IN MYELOID CELLS",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:38Z",
  "url": "https://research.draconitic.com/paper/em9p72p1z66vg",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}