RHOC MODULATES P53 SIGNALING AND APOPTOSIS IN MYELOID CELLS

@article{rodrigues2026rhoc,
  title = {{RHOC MODULATES P53 SIGNALING AND APOPTOSIS IN MYELOID CELLS}},
  author = {Beatriz Almeida RODRIGUES and Adriana Da Silva Santos DUARTE and Sara Teresinha OLALLA SAAD and Mariana LAZARINI},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107683},
  url = {https://doi.org/10.1016/j.htct.2026.107683},
  note = {CC BY},
}

TY  - JOUR
TI  - RHOC MODULATES P53 SIGNALING AND APOPTOSIS IN MYELOID CELLS
AU  - Beatriz Almeida RODRIGUES
AU  - Adriana Da Silva Santos DUARTE
AU  - Sara Teresinha OLALLA SAAD
AU  - Mariana LAZARINI
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107683
UR  - https://doi.org/10.1016/j.htct.2026.107683
AB  - Background: Dysregulation of the p53 signaling pathway plays a critical role in the pathophysiology of acute myeloid leukemia (AML) and is associated with disease progression, therapeutic resistance, and poor clinical outcome. As the master regulator of the DNA damage response, p53 controls processes such as DNA repair, cell-cycle arrest, and apoptosis. Although RHO GTPases are classically associated with cytoskeletal organization, they also participate in genotoxic stress responses and genomic stability. RHOC has been identified as a transcriptional target of p53 and may contribute to cell survival following DNA damage. However, its role in modulating p53 activation and apoptosis in AML remains unclear. Aim: To investigate the role of RHOC in p53 signaling and apoptosis in acute myeloid leukemia cell line. Materials and methods: OCI-AML3 cells were transduced with a non-targeting shRNA (shCTRL) or an RHOC-targeting shRNA (shRHOC). RHOC silencing was confirmed by RT-qPCR. To induce p53 activation, cells were exposed to 20 J/m² UVC radiation. p53 protein expression was assessed by flow cytometry 4 h after irradiation (n=4). The expression of BCL-2, BCL-XL, MCL-1, BAX, BAD, BIM, PUMA, and NOXA was analyzed by RT-qPCR. Apoptosis was evaluated by Annexin V/propidium iodide staining at 6 and 24 h after irradiation. Results: Under basal conditions, p53 protein expression was significantly higher in shRHOC than in shCTRL cells, with mean fluorescence intensity values of 23.55 ± 4.42 and 15.39 ± 2.28, respectively (P<0.05). UVC exposure increased p53 expression in both groups. Four hours after irradiation, p53 expression remained significantly higher in shRHOC cells than in shCTRL cells (87.93 ± 27.24 versus 62.64 ± 18.17, P<0.05). In the absence of UVC, BAX expression was reduced by approximately 50%, whereas NOXA expression was approximately threefold higher in shRHOC than in shCTRL cells. UVC exposure reduced BCL-2, BCL-XL, and BIM expression and tended to increase MCL-1 in both groups. Following irradiation, shRHOC cells exhibited higher expression of BAD, BAX, PUMA, and NOXA than shCTRL cells. Basal apoptosis was low in both groups. Six hours after UVC exposure, total apoptosis was higher in shCTRL than in shRHOC cells (34.04 ± 0.64% vs. 24.26 ± 5.54%). After 24 h, distinct cell death profiles were observed. In shCTRL cells, the reduction in total apoptosis (20.58 ± 7.49%) was accompanied by an increased Annexin V−/PI+ population (24.70 ± 1.27%), consistent with necrosis. In contrast, shRHOC cells maintained a higher proportion of late apoptotic cells (16.90 ± 6.22%) and a lower frequency of Annexin V−/PI+ cells (13.55 ± 5.02%). Discussion and conclusion: RHOC silencing was associated with increased p53 expression, induction of pro-apoptotic genes following UVC exposure, and enhanced late apoptosis, suggesting that RHOC contributes to the cellular adaptation to genotoxic stress in myeloid cells. These findings support a role for RHOC as a modulator of the p53 signaling pathway and apoptosis in AML. Funding: FAPESP.
SN  - 2531-1379
SN  - 2531-1387
ER  -