Rac GTPases in acute myeloid leukemia cells: Expression profile and biological effects of pharmacological inhibition

Ramos, Débora Felícia Vieira; Mancuso, Rubia Isler; Contieri, Bruna; Duarte, Adriana da Silva Santos; Paiva, Lucilene Betega de; Carrilho, Jeferson de Melo; Saad, Sara Teresinha Olalla; Lazarini, Mariana

doi:10.1016/j.taap.2022.115990

Cited by 10 publications

(7 citation statements)

References 72 publications

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“…Compared with normal tissues, Rac3 mRNA levels were significantly overexpressed in BLCA, CESC, DLBC, HNSC, LIHC, LUAD, LUSC, OV, PAAD, PRAD, SKCM, THCA, THYM, UCEC, and UCS, while it was underexpressed in KIRC and LAML. The results were further supported by previous studies involving in bladder cancer [10], [11], lung adenocarcinoma [14], [38], breast cancer [39], [40], prostate carcinomas [41], brain tumors [42], colitis-associated cancer [43], and acute myeloid leukemia [44]. Moreover, the protein expression of Rac3 was highly expressed in lung cancer, head and neck cancer, liver cancer, urothelial cancer, breast cancer, cervical cancer, ovarian cancer, lymphoma, and skin cancer from the HPA database.…”

Section: Discussionsupporting

confidence: 86%

“…Recent studies revealed that Rac3 was overexpressed by confirmed with qRT-PCR and western blot results and indicated a poor prognosis in bladder cancer [10], [45]. Ramos et al revealed that Rac3 levels were increased in AML compared with healthy donors [44]. Rac3 was overexpressed and associated with more prolonged survival in LUAD patients [38], [46].…”

Section: Discussionmentioning

confidence: 88%

“…Compared with the existing works, our study not only expanded the understanding of the Rac3 roles in pan cancers but also obtained new meaningful findings. Previous research that investigated differential expression of Rac3 focused on a single type of cancer, such as acute myeloid leukemia [44], bladder cancer [10], colitis-associated cancer [43], and lung Adenocarcinoma [38]. However, Pan-cancer analysis can provide a comprehensive insight into the Rac3 roles.…”

Section: Discussionmentioning

confidence: 99%

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Multiple Omics Analysis of the Rac3 Roles in Different Types of Human Cancer

Song

2022

IEEE Access

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Rac Family Small GTPase 3 (Rac3) is a member of the Rho family of small GTP-binding proteins which play critical roles in the occurrence, progression, and metastasis of various tumors. Nevertheless, previous studies have focused on a single type of human cancer, so that the roles of Rac3 in different cancer types have not been sufficiently clarified. With the progress of biological detection and bioinformatics technology, the emerging cancer genomics databases make it possible to perform a pancancer analysis. Therefore, for the first time, we performed multiple omics analysis to investigate the roles of Rac3 in differential expression, survival prognosis, mutative status, DNA methylation, functions, immune infiltration, and immunotherapy across 33 human cancer types. We found that Rac3 expression was abnormal in 17 cancer types and significantly different in both molecular and immune subtypes of 10 cancers (p<0.05). These Rac3 expression dysregulations in cancer tissues significantly affected their corresponding survival prognosis. Our results also indicated that genetic alterations of Rac3 occurred in 27 cancer types and were significantly associated with prognosis. Moreover, methylation of Rac3 was associated with dysfunctional T-cell phenotypes and affected the prognosis of the brain, melanoma, and breast tumors, and Rac3 Copy Number Alterations (CNA) might affect the infiltration levels of different immune cells in nine cancers. Rac3 and Rac3-related genes were enriched in the axon guidance, actin cytoskeleton regulation, and neurotrophin signaling pathway, and involved the regulation of cellular localization and actin cytoskeleton organization, and small GTPase mediated signal transduction. Then, we further explored the correlations between Rac3 expression and 25 immune cells and cancer-associated fibroblasts across 33 human cancers. Furthermore, we found that Rac3 achieved higher predictive power (AUC>0.5) than three standardized biomarkers of tumor immune responses and was associated with cytotoxic T-cell levels (CTLs) and the risk of immunotherapeutic responses in three cancer types. Collectively, our study contributes to a comprehensive and integrative understanding of the oncogenic roles of Rac3 across human cancers and offers a new clue for treatment strategies.INDEX TERMS Rac3, human cancer, multiple omics, cancer prognosis, immune infiltrating.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Multiple Omics Analysis of the Rac3 Roles in Different Types of Human Cancer

Song

2022

IEEE Access

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“… 33 , 49 , 50 This process-dependent variability is also exemplified by cell death. While significant increases in apoptotic OCI-AML3 human acute myeloid leukemia and bladder smooth muscle cells were observed after treatment with 30 μM and 50 μM EHT1864, respectively, 51 , 52 rat HBCs in vehicle- and 50 μM EHT1864-treated cultures demonstrated similar morphological appearances ( Figures 4 A–4D, 4F, and 4I) and treated mouse platelets retained significant viability up to 200 μM EHT1864. 53 …”

Section: Discussionmentioning

confidence: 90%

Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration

Louie,

Barrios-Camacho,

Bromberg

et al. 2024

iScience

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“…Early research indicated that inactivation of RAC1-GTPase suppressed migration and promoted drug induced apoptosis in KG-1 cells ( 37 ). Recent in vitro studies found that suppression of RAC with a RAC inhibitor (EHT-1864) could increase autophagy, apoptosis, cell cycle, modulation of p53 factor and inhibit the PI3K/AKT/mTOR signaling pathway in AML cell lines ( 38 ). In fact, it has recently been reported that the combination of EHT-1846, venetoclax(BCL-2 inhibitor) and midostaurin(FLT3 inhibitor) could reverse midostaurin resistance in AML cells ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of autophagy-associated genes and prognostic implications in adults with acute myeloid leukemia by integrated bioinformatics analysis

2023

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Acute myeloid leukemia (AML) is one of the most common malignant blood neoplasma in adults. The prominent disease heterogeneity makes it challenging to foresee patient survival. Autophagy, a highly conserved degradative process, played indispensable and context-dependent roles in AML. However, it remains elusive whether autophagy-associated stratification could accurately predict prognosis of AML patients. Here, we developed a prognostic model based on autophagy-associated genes, and constructed scoring systems that help to predicte the survival of AML patients in both TCGA data and independent AML cohorts. The Nomogram model also confirmed the autophagy-associated model by showing the high concordance between observed and predicted survivals. Additionally, pathway enrichment analysis and protein-protein interaction network unveiled functional signaling pathways that were associated with autophagy. Altogether, we constructed the autophagy-associated prognostic model that might be likely to predict outcome for AML patients, providing insights into the biological risk stratification strategies and potential therapeutic targets.

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Rac GTPases in acute myeloid leukemia cells: Expression profile and biological effects of pharmacological inhibition

Cited by 10 publications

References 72 publications

Multiple Omics Analysis of the Rac3 Roles in Different Types of Human Cancer

Multiple Omics Analysis of the Rac3 Roles in Different Types of Human Cancer

Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration

Identification of autophagy-associated genes and prognostic implications in adults with acute myeloid leukemia by integrated bioinformatics analysis

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