The role of ARHGAP9: clinical implication and potential function in acute myeloid leukemia

Han, Caixia; He, Shujiao; Wang, Ruiqi; Gao, Xuefeng; Wang, Hong; Qiao, Jingqiao; Meng, Xiangyu; Li, Yonghui; Yu, Li

doi:10.1186/s12967-021-02733-5

Cited by 13 publications

(7 citation statements)

References 55 publications

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“…Despite the significantly lower expression of ARHGEF6 in CN-AML, no relationship between ARHGEF6 expression and CN-AML prognosis has been found. Furthermore, several researchers found that some genes, for example, ARHGAP9 and BCL2 were correlated with the prognosis of auto/allo-HSCT and/or chemotherapy in AML patients [3,4]. Our findings showed that auto/allo-HSCT significantly improves prognosis in patients with low ARHGEF6 expression.…”

Section: Plos Onesupporting

confidence: 57%

“…On the other hand, ARHGAP9, which belongs to the Rho GAP family, inactivates GTPases and oppositely function to that of Rho GEFs. ARHGAP9 is an adverse prognostic factor for AML OS [3]. Thus, Rho GEFs and Rho GAPs may play other roles in cancers.…”

Section: Plos Onementioning

confidence: 99%

“…In the United States, 75% of AML patients are over 65 years old, elder patients are refractory and prone to relapse, the recurrence rate can reach 10%-40% even in younger patients [1,2]. Recently, several studies have shown that AML patients with some genes (such as ARHGAP9 and BCL2) abnormal expression can benefit from auto/allo-HSCT [3,4]. Therefore, optimal therapeutic strategy based on validated prognostic markers is important for AML patients.…”

Section: Introductionmentioning

confidence: 99%

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Clinical implication and potential function of ARHGEF6 in acute myeloid leukemia: An in vitro study

Wang

Yang

et al. 2023

PLoS ONE

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The roles of Rho GTPases in various types of cancer have been extensively studied, but the research of Rho guanine nucleotide exchange factors (GEFs) in cancer is not comprehensive. Rho guanine nucleotide exchange factor 6 (ARHGEF6) is an important member of the Rho GEFs family involved in cytoskeletal rearrangement, and it has not been investigated in acute myeloid leukemia (AML). Our research showed that the expression of ARHGEF6 was mainly higher in AML cell lines, meanwhile, was highest in the samples from patients with AML compared to other cancer types. High ARHGEF6 expression in AML was associated with a good prognosis. ARHGEF6low cases showed significantly higher overall survival (OS) after autologous or allogeneic HSCT (auto/allo-HSCT). High expression of ARHGEF6 downregulates the negative regulation of myeloid differentiation process and upregulates G protein-coupled receptor signaling pathway-related processes, among which HOXA9, HOXB6, and TRH have significant differential expression and prognostic impact in AML. Therefore, ARHGEF6 can become a prognostic marker in AML; ARHGEF6low patients can gain from auto/allo-HSCT.

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Section: Plos Onesupporting

confidence: 57%

Section: Plos Onementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical implication and potential function of ARHGEF6 in acute myeloid leukemia: An in vitro study

Wang

Yang

et al. 2023

PLoS ONE

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“…Metascape ( http://metascape.org/gp/ ) is a gene-annotation and analysis tool commonly used in genetic research. ( Zhou et al, 2019 ; Han et al, 2021 ; Ye et al, 2021 ). The Metascape database was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses NMRGs.…”

Section: Methodsmentioning

confidence: 99%

Identification of NAD+ Metabolism-Derived Gene Signatures in Ovarian Cancer Prognosis and Immunotherapy

et al. 2022

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Background: Nicotinamide adenine dinucleotide (NAD+) has emerged as a critical regulator of cell signaling and survival pathways, affecting tumor initiation and progression. In this study it was investigated whether circulating NAD+ metabolism-related genes (NMRGs) could be used to predict immunotherapy response in ovarian cancer (OC) patients.Method: In this study, NMRGs were comprehensively examined in OC patients, three distinct NMRGs subtypes were identified through unsupervised clustering, and an NAD+-related prognostic model was generated based on LASSO Cox regression analysis and generated a risk score (RS). ROC curves and an independent validation cohort were used to assess the model’s accuracy. A GSEA enrichment analysis was performed to investigate possible functional pathways. Furthermore, the role of RS in the tumor microenvironment, immunotherapy, and chemotherapy was also investigated.Result: We found three different subgroups based on NMRGs expression patterns. Twelve genes were selected by LASSO regression to create a prognostic risk signature. High-RS was founded to be linked to a worse prognosis. In Ovarian Cancer Patients, RS is an independent prognostic marker. Immune infiltrating cells were considerably overexpressed in the low-RS group, as immune-related functional pathways were significantly enriched. Furthermore, immunotherapy prediction reveal that patients with low-RS are more sensitive to immunotherapy.Conclusion: For a patient with OC, NMRGs are promising biomarkers. Our prognostic signature has potential predictive value for OC prognosis and immunotherapy response. The results of this study may help improve our understanding of NMRG in OCs.

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“…To our surprise, a study concerning on the role of ARHGAP9 in clinical AML was just published. This study concluded that ARHGAP9 was highly expressed in AML patients associated with poor overall survival and could be used as a prognostic biomarker (Han et al, 2021). However, more biological functions of ARHGAP9 in the occurrence and development of AML remain unclear, which need an in‐depth research.…”

Section: Introductionmentioning

confidence: 99%

SOX4‐induced upregulation of ARHGAP9 promotes the progression of acute myeloid leukemia

Zou

Wang

2021

Drug Development Research

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Acute myeloid leukemia (AML) is the most common acute leukemia. Rho GTPase activating protein 9 (ARHGAP9) has been reported to be positively correlated with overall survival of AML patients, but the specific molecular function remains unclear. This study aims to further explore the functional role and the molecular mechanism of ARHGAP9 in AML cells. The expression level of ARHGAP9 in AML cells was measured using quantitative real‐time PCR (qRT‐PCR) and western blot. Cell transfection was performed to interfere ARHGAP9. CCK‐8, flow cytometry and TUNEL assays were conducted to detect cell viability, cell cycle distribution and apoptosis, respectively. The binding relationship between SOX4 and ARHGAP9 promoter was verified using luciferase reporter assay and chromatin immunoprecipitation. The results showed that ARHGAP9 was upregulated in AML cells. Interference of ARHGAP9 greatly reduced cell viability and induced cell cycle arrest in G1 phase, accompanied with the reduction of Ki67, PCNA, cyclin D1, cyclin E1, CDK4 and CDK6. In addition, Interference of ARHGAP9 greatly promoted cell apoptosis, accompanied with the decreased protein expression of Bcl‐2 and the increased protein expression of Bax, cleaved caspase 3 and cleaved caspase 9. Furthermore, SOX4 directly bound to ARHGAP9 promoter and regulated ARHGAP9 expression. In conclusion, this study suggested that ARHGAP9 interference exerted an anti‐tumor effect through inhibiting cell proliferation, blocking cell cycle progression, and promoting cell apoptosis in AML cells. ARHGAP9 may serve as a novel therapeutic target for AML.

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The role of ARHGAP9: clinical implication and potential function in acute myeloid leukemia

Cited by 13 publications

References 55 publications

Clinical implication and potential function of ARHGEF6 in acute myeloid leukemia: An in vitro study

Clinical implication and potential function of ARHGEF6 in acute myeloid leukemia: An in vitro study

Identification of NAD+ Metabolism-Derived Gene Signatures in Ovarian Cancer Prognosis and Immunotherapy

SOX4‐induced upregulation of ARHGAP9 promotes the progression of acute myeloid leukemia

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