DEPDC1 drives hepatocellular carcinoma cell proliferation, invasion and angiogenesis by regulating the CCL20/CCR6 signaling pathway

Guo, Wubin; Li, Hui; Liu, Huan; Ma, Xin; Yang, Sijin; Wang, Ziwei

doi:10.3892/or.2019.7221

Cited by 20 publications

(24 citation statements)

References 35 publications

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“…no. C0078S; Beyotime Institute of Biotechnology), according to the manufacturer's protocol ( 29 ). Positive cells were observed under an Olympus IX71 fluorescent microscope (Olympus Corp, Tokyo, Japan; magnification ×200) and analyzed using Image J software (NIH, Bethesda, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation

Qiu

Zhang

et al. 2021

Front. Cardiovasc. Med.

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Background: The beneficial effects of parasympathetic stimulation in pulmonary arterial hypertension (PAH) have been reported. However, the specific mechanism has not been completely clarified. Donepezil, an oral cholinesterase inhibitor, enhances parasympathetic activity by inhibiting acetylcholinesterase, whose therapeutic effects in PAH and its mechanism deserve to be investigated.Methods: The PAH model was established by a single intraperitoneal injection of monocrotaline (MCT, 50 mg/kg) in adult male Sprague-Dawley rats. Donepezil was administered via intraperitoneal injection daily after 1 week of MCT administration. At the end of the study, PAH status was confirmed by echocardiography and hemodynamic measurement. Testing for acetylcholinesterase activity and cholinergic receptor expression was used to evaluate parasympathetic activity. Indicators of pulmonary arterial remodeling and right ventricular (RV) dysfunction were assayed. The proliferative and apoptotic ability of pulmonary arterial smooth muscle cells (PASMCs), inflammatory reaction, macrophage infiltration in the lung, and activation of bone marrow-derived macrophages (BMDMs) were also tested. PASMCs from the MCT-treated rats were co-cultured with the supernatant of BMDMs treated with donepezil, and then, the proliferation and apoptosis of PASMCs were evaluated.Results: Donepezil treatment effectively enhanced parasympathetic activity. Furthermore, it markedly reduced mean pulmonary arterial pressure and RV systolic pressure in the MCT-treated rats, as well as reversed pulmonary arterial remodeling and RV dysfunction. Donepezil also reduced the proliferation and promoted the apoptosis of PASMCs in the MCT-treated rats. In addition, it suppressed the inflammatory response and macrophage activation in both lung tissue and BMDMs in the model rats. More importantly, donepezil reduced the proliferation and promoted the apoptosis of PASMCs by suppressing M2-macrophage activation.Conclusion: Donepezil could prevent pulmonary vascular and RV remodeling, thereby reversing PAH progression. Moreover, enhancement of the parasympathetic activity could reduce the proliferation and promote the apoptosis of PASMCs in PAH by suppressing M2-macrophage activation.

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Section: Methodsmentioning

confidence: 99%

Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation

Qiu

Zhang

et al. 2021

Front. Cardiovasc. Med.

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“…17 On the other hand, CCL20 contributes to liver fibrosis 19,20 and angiogenesis in malignant tumors. [21][22][23] Thus, CCL20 appears to be involved in autoimmunity/inflammation, vasculopathy and tissue fibrosis, which are the 3 cardinal pathological features of SSc. 2,3,24 Based on these backgrounds, we examined if CCL20 is involved in the development of SSc-associated symptoms and complications.…”

Section: Introductionmentioning

confidence: 99%

Association of serum CCL20 levels with pulmonary vascular involvement and primary biliary cholangitis in patients with systemic sclerosis

et al. 2021

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Aim: Systemic sclerosis (SSc) is a chronic autoimmune disease resulting in vasculopathy and fibrosis of the skin and major internal organs. Especially, interstitial lung disease and pulmonary arterial hypertension are the leading causes of mortality. C-C motif ligand 20 (CCL20) is known as a homeostatic and inflammatory chemokine, which is associated with fibrosis and angiogenesis and constantly expressed in organs involved in SSc. Therefore, we investigated the potential contribution of CCL20 to the development of SSc. Method:We conducted cross-sectional analyses of 67 SSc patients and 20 healthy controls recruited in a single center for 9 years. Serum CCL20 levels were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed with the Mann-Whitney U test, the Kruskal-Wallis test followed by Dunn's multiple comparison test, Fisher's exact probability test and the Spearman's rank correlation coefficient.Results: SSc patients had significantly higher serum CCL20 levels than healthy controls. In SSc patients, serum CCL20 levels correlated inversely with the percentage of predicated diffusion lung capacity for carbon monoxide and positively with mean pulmonary artery pressure (mPAP). In addition, SSc patients with increased serum CCL20 levels had anti-mitochondrial antibody M2 titer significantly elevated relative to those with normal levels, and SSc patients with asymptomatic primary biliary cholangitis (PBC) possessed higher serum CCL20 levels than those without. Importantly, serum CCL20 levels were associated positively with mPAP values and PBC presence by multivariate regression analysis. Conclusion:Serum CCL20 levels may be involved in the development of pulmonary vascular involvement leading to pulmonary arterial hypertension and asymptomatic PBC in SSc patients.

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“…In another study, data showed that CEPP55 facilitates the EMT process in renal cells and participates in the AKT pathway [42,43]. DEPDC1 has been identified in various cancers, including HCC, breast cancer, and prostate cancer, among others and is positively involved with multiple tumorous biological processes, including proliferation, invasion, and angiogenesis by activating different signaling pathways, such as CCL20/CCR6, E2F et al [44][45][46]. According to previous reports, CLSPN is overexpressed in renal cell carcinoma (RCC) as assessed by immunohistochemistry in 95 RCC cases.…”

Section: Discussionmentioning

confidence: 99%

Identification of Prognostic Biomarkers and Correlation with Immune Infiltrates in Hepatocellular Carcinoma Based on a Competing Endogenous RNA Network

Zhu

Wang

et al. 2020

Preprint

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Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Recently, competing endogenous RNAs (ceRNA) have revealed a significant role in the progression of HCC. Herein, we aimed to construct a ceRNA network to identify potential biomarkers and illustrate its correlation with immune infiltration in HCC. Methods: RNA sequencing data and clinical traits of HCC patients were downloaded from TCGA. The limma R package was used to identify differentially expressed (DE) RNAs. The predicted prognostic model was established using univariate and multivariate Cox regression. A K-M curve and GEPIA website were utilized for survival analysis. Functional annotation was determined using Enrichr and Reactome. Protein-to-protein network analysis was implemented using SRTNG and Cytoscape. Hub gene expression was validated by Oncomine and the Hunan Protein Atlas database. Immune infiltration was analyzed by TIMMER, and Drugbank was exploited to identify bioactive compounds. Results: The predicted model that was established revealed significant efficacy with 3- and 5-years of the area under ROC at 0.804 and 0.744, respectively. Eleven DEmiRNAs were screened out by a K-M survival analysis. Then, we constructed a ceRNA network, including 56 DElncRNAs, 6 DEmiRNAs, and 28 DEmRNAs. The 28 DEmRNAs were enriched in cancer-related pathways, for example, the TNF signaling pathway. Moreover, six hub genes, CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1, were all overexpressed in HCC tissues and independently correlated with survival rate. Furthermore, expression of hub genes was related to immune cell infiltration in HCC, including B cells, CD8 + T cells, CD4 + T cells, monocytes, macrophages, neutrophils, and dendritic cells. Conclusions: The findings from this study demonstrate that CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1 are closely associated with prognosis and immune infiltration, representing potential therapeutic targets or prognostic biomarkers in HCC.

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DEPDC1 drives hepatocellular carcinoma cell proliferation, invasion and angiogenesis by regulating the CCL20/CCR6 signaling pathway

Cited by 20 publications

References 35 publications

Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation

Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation

Association of serum CCL20 levels with pulmonary vascular involvement and primary biliary cholangitis in patients with systemic sclerosis

Identification of Prognostic Biomarkers and Correlation with Immune Infiltrates in Hepatocellular Carcinoma Based on a Competing Endogenous RNA Network

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