&lt;p&gt;High expression of dedicator of cytokinesis 1 adversely influences the prognosis of acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation&lt;/p&gt;

Zhang, Gaoqi; Zhang, Jilei; Yang, Xinrui; Zhang, Xinpei; Yang, Siyuan; Wang, Jing; Hu, Kai; Shi, Jianxin; Ke, Xiaoyan; Fu, Lin

doi:10.2147/cmar.s192845

Cited by 2 publications

(2 citation statements)

References 27 publications

(32 reference statements)

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“…In the present study, we focused on the hub gene TRIM32 since both DOCK1 and GLI2 had been discussed as adverse prognostic markers of AML in previous articles ( 31 – 34 ). To the best of our knowledge, it is the first time to report and validate the role of TRIM32 in AML.…”

Section: Discussionmentioning

confidence: 99%

Up-Regulation of TRIM32 Associated With the Poor Prognosis of Acute Myeloid Leukemia by Integrated Bioinformatics Analysis With External Validation

Yang

et al. 2022

Front. Oncol.

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BackgroundAcute myeloid leukemia (AML) is a malignant and molecularly heterogeneous disease. It is essential to clarify the molecular mechanisms of AML and develop targeted treatment strategies to improve patient prognosis.MethodsAML mRNA expression data and survival status were extracted from TCGA and GEO databases (GSE37642, GSE76009, GSE16432, GSE12417, GSE71014). Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis were performed. Functional enrichment analysis and protein-protein interaction (PPI) network were used to screen out hub genes. In addition, we validated the expression levels of hub genes as well as the prognostic value and externally validated TRIM32 with clinical data from our center. AML cell lines transfected with TRIM32 shRNA were also established to detect the proliferation in vitro.ResultsA total of 2192 AML patients from TCGA and GEO datasets were included in this study and 20 differentially co-expressed genes were screened by WGCNA and differential gene expression analysis methods. These genes were mainly enriched in phospholipid metabolic processes (biological processes, BP), secretory granule membranes (cellular components, CC), and protein serine/threonine kinase activity (molecular functions, MF). In addition, the protein-protein interaction (PPI) network contains 15 nodes and 15 edges and 10 hub genes (TLE1, GLI2, HDAC9, MICALL2, DOCK1, PDPN, RAB27B, SIX3, TRIM32 and TBX1) were identified. The expression of 10 central genes, except TLE1, was associated with survival status in AML patients (p<0.05). High expression of TRIM32 was tightly associated with poor relapse-free survival (RFS) and overall survival (OS) in AML patients, which was verified in the bone marrow samples from our center. In vitro, knockdown of TRIM32 can inhibit the proliferation of AML cell lines.ConclusionTRIM32 was associated with the progression and prognosis of AML patients and could be a potential therapeutic target and biomarker for AML in the future.

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Section: Discussionmentioning

confidence: 99%

Up-Regulation of TRIM32 Associated With the Poor Prognosis of Acute Myeloid Leukemia by Integrated Bioinformatics Analysis With External Validation

Yang

et al. 2022

Front. Oncol.

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“…as a rac-specific GEF, DOCK1 regulates phagocytosis, myoblastic fusion, cell migration and circular dorsal fold formation (9,10). Abnormal expression and activity of DOCK1 is associated with the malignant characteristics of multiple tumors (11)(12)(13)(14). increasing evidence has indicated that docK1 regulates invasion and metastasis by acting on downstream receptor tyrosine kinases (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

TBOPP enhances the anticancer effect of cisplatin by inhibiting DOCK1 in renal cell carcinoma

et al. 2020

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The treatment of renal cell carcinoma (rcc) with chemotherapy remains a challenge; therefore, improving the knowledge of the molecular mechanisms underlying rcc chemoresistance and developing novel therapeutic strategies is important. Dedicator of cytokinesis 1 (DOCK1), the first member of the DOCK family to be discovered, displays various roles during tumorigenesis; however, its role during rcc progression is not completely understood. Therefore, the present study aimed to clarify the function of DOCK1 and 1-[2-(3'-(trifluorom ethyl)-(1,1'-biphenyl)-4-yl)-2-oxoethyl]-5-pyrrolidinylsulfonyl-2 (1H)-pyridone (TBOPP), a DOCK1-sensitive inhibitor, during rcc development and chemoresistance. The results of ccK-8 and edu assay indicated that TBoPP decreased rcc cell viability and proliferation compared with the control group, and sensitized rcc cells to cisplatin. Moreover, rcc cells with high DOCK1 expression levels displayed increased resistance to cisplatin, whereas docK1 knockdown enhanced the lethal effects of cisplatin on rcc cells. Furthermore, the results determined by western blotting, CCK-8 and cell apoptosis assay indicated that TBoPP effectively reduced docK1 expression levels compared with the control group, and the TBOPP-mediated cisplatin sensitizing effect was mediated by DOCK1 inhibition. The present study suggests that DOCK1 plays a vital role in rcc cell chemoresistance to cisplatin; therefore, TBoPP may serve as a novel therapeutic agent for rcc chemoresistance.

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<p>High expression of dedicator of cytokinesis 1 adversely influences the prognosis of acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation</p>

Cited by 2 publications

References 27 publications

Up-Regulation of TRIM32 Associated With the Poor Prognosis of Acute Myeloid Leukemia by Integrated Bioinformatics Analysis With External Validation

Up-Regulation of TRIM32 Associated With the Poor Prognosis of Acute Myeloid Leukemia by Integrated Bioinformatics Analysis With External Validation

TBOPP enhances the anticancer effect of cisplatin by inhibiting DOCK1 in renal cell carcinoma

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