The role of GTPase-activating protein ARHGAP26 in human cancers

Zhang, Lingye; Zhou, Anni; Zhu, Shoumin; Min, Li; Liu, Si; Li, Peng; Zhang, Shutian

doi:10.1007/s11010-021-04274-3

Cited by 7 publications

(7 citation statements)

References 63 publications

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“…Rho GTPases have been demonstrated to influence diseased cell invasion and metastasis by controlling cytoskeletal contraction and cell membrane protrusion [ 28 ]. Negative regulators of Rac/Rho-like GTPases, GTPase-activating proteins (GAPs), reduce Rho GTPase activity by boosting the hydrolytic ability of Rho GTPases to convert activated GTP-binding status to inactivated GDP-binding status [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Relationship between the expression of ARHGAP25 and RhoA in non-small cell lung cancer and vasculogenic mimicry

Shi

Jia

et al. 2022

BMC Pulm Med

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Background Vasculogenic mimicry (VM) is a recently identified pattern of blood supply to tumor tissue. It has long been considered a functional element in the metastasis and prognosis of malignant tumors. Both Rho GTPase-activating protein 25 (ARHGAP25) and Ras homolog family member A (RhoA) are effective predictors of tumor metastasis. In this study, we examined the expression levels of ARHGAP25 and RhoA and the structure of VM in non-small cell lung cancer (NSCLC). At the same time, we used cytology-related experiments to explore the effect of ARHGAP25 on the migration ability of tumor cells. Furthermore, we analyzed the interaction between the three factors and their association with clinicopathological characteristics and the five-year survival time in patients using statistical tools. Methods A total of 130 well-preserved NSCLC and associated paracancerous tumor-free tissues were obtained. Cell colony formation, wound healing, and cytoskeleton staining assays were used to analyze the effect of ARHGAP25 on the proliferation and migration ability of NSCLC cells. Immunohistochemical staining was used to determine the positivity rates of ARHGAP25, RhoA, and VM. Statistical software was used to examine the relationships between the three factors and clinical case characteristics, overall survival, and disease-free survival. Results Cell colony formation, wound healing, and cytoskeleton staining assays confirmed that ARHGAP25 expression affects the proliferation and migratory abilities of NSCLC cells. ARHGAP25 positivity rates in NSCLC and paracancerous tumor-free tissues were 48.5% and 63.1%, respectively, whereas RhoA positivity rates were 62.3% and 18.5%, respectively. ARHGAP25 had a negative relationship with RhoA and VM, whereas RhoA and VM had a positive relationship (P < 0.05). ARHGAP25, RhoA, and VM affected the prognosis of patients with NSCLC (P < 0.05) according to Kaplan–Meier of survival time and Cox regression analyses. Furthermore, lowering ARHGAP25 expression increased NSCLC cell proliferation and migration. Conclusions ARHGAP25 and RhoA expression is associated with VM and may be of potential value in predicting tumor metastasis, prognosis, and targeted therapy.

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Section: Discussionmentioning

confidence: 99%

Relationship between the expression of ARHGAP25 and RhoA in non-small cell lung cancer and vasculogenic mimicry

Shi

Jia

et al. 2022

BMC Pulm Med

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“…Similarly, in BTZ-resistant cells, we observed hypermethylation in the ARHGAP26 gene, which is involved in tumorigenesis and progression of human cancers. However, in various types of cancer, its expression changes significantly [ 29 ]. For instance, Qian et al demonstrated that ARHGAP26 hypermethylation resulted in reduced gene expression, which may be an early event in the pathogenesis of AML.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D and K Supplementation Is Associated with Changes in the Methylation Profile of U266-Multiple Myeloma Cells, Influencing the Proliferative Potential and Resistance to Bortezomib

Łuczkowska,

Kulig,

Baumert

et al. 2023

Nutrients

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Multiple myeloma (MM) is a plasma cell malignancy that, despite recent advances in therapy, continues to pose a major challenge to hematologists. Currently, different classes of drugs are applied to treat MM, among others, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Most of them participate in an interplay with the immune system, hijacking its effector functions and redirecting them to anti-MM activity. Therefore, adjuvant therapies boosting the immune system may be potentially beneficial in MM therapy. Vitamin D (VD) and vitamin K (VK) have multiple so called “non-classical” actions. They exhibit various anti-inflammatory and anti-cancer properties. In this paper, we investigated the influence of VD and VK on epigenetic alterations associated with the proliferative potential of MM cells and the development of BTZ resistance. Our results showed that the development of BTZ resistance is associated with a global decrease in DNA methylation. On the contrary, both control MM cells and BTZ-resistant MM cells exposed to VD alone and to the combination of VD and VK exhibit a global increase in methylation. In conclusion, VD and VK in vitro have the potential to induce epigenetic changes that reduce the proliferative potential of plasma cells and may at least partially prevent the development of resistance to BTZ. However, further ex vivo and in vivo studies are needed to confirm the results and introduce new supplementation recommendations as part of adjuvant therapy.

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“…Our findings suggest that there are more genes with reduced expression than increased expression. We observed increased 5hmC levels in H3K4me3 regions in genes relating to cell proliferation, such as CDK6 [ 37 ] and ZMYND8 [ 38 ], and reduced 5hmC levels in H3K4me3 regions in genes that may be related to tumor suppression, such as ARHGAP26 [ 39 ] and GLI3 [ 40 ]. These results indicate that aberrant 5hmC levels result in unbalanced gene expression, which is an important mechanism of leukemogenesis.…”

Section: Discussionmentioning

confidence: 99%

Classification of Acute Myeloid Leukemia by Cell-Free DNA 5-Hydroxymethylcytosine

Shao

Shah

Ganguly

et al. 2023

Genes

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Epigenetic abnormality is a hallmark of acute myeloid leukemia (AML), and aberrant 5-hydroxymethylcytosine (5hmC) levels are commonly observed in AML patients. As epigenetic subgroups of AML correlate with different clinical outcomes, we investigated whether plasma cell-free DNA (cfDNA) 5hmC could categorize AML patients into subtypes. We profiled the genome-wide landscape of 5hmC in plasma cfDNA from 54 AML patients. Using an unbiased clustering approach, we found that 5hmC levels in genomic regions with a histone mark H3K4me3 classified AML samples into three distinct clusters that were significantly associated with leukemia burden and survival. Cluster 3 showed the highest leukemia burden, the shortest overall survival of patients, and the lowest 5hmC levels in the TET2 promoter. 5hmC levels in the TET2 promoter could represent TET2 activity resulting from mutations in DNA demethylation genes and other factors. The novel genes and key signaling pathways associated with aberrant 5hmC patterns could add to our understanding of DNA hydroxymethylation and highlight the potential therapeutic targets in AML. Our results identify a novel 5hmC-based AML classification system and further underscore cfDNA 5hmC as a highly sensitive marker for AML.

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The role of GTPase-activating protein ARHGAP26 in human cancers

Cited by 7 publications

References 63 publications

Relationship between the expression of ARHGAP25 and RhoA in non-small cell lung cancer and vasculogenic mimicry

Relationship between the expression of ARHGAP25 and RhoA in non-small cell lung cancer and vasculogenic mimicry

Vitamin D and K Supplementation Is Associated with Changes in the Methylation Profile of U266-Multiple Myeloma Cells, Influencing the Proliferative Potential and Resistance to Bortezomib

Classification of Acute Myeloid Leukemia by Cell-Free DNA 5-Hydroxymethylcytosine

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