Apoptosis-related protein-1 acts as a tumor suppressor in cholangiocarcinoma cells by inducing cell cycle arrest via downregulation of cyclin-dependent kinase subunits

Zheng, Jun; Li, Qinlong; Wang, Yingmei; Fu, Xin; Wang, Wenyong; Fan, Linni; Yan, Wei

doi:10.3892/or.2015.4422

Cited by 17 publications

(15 citation statements)

References 39 publications

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“…MAGEH1 expression has been reported to be downregulated in hepatocellular carcinoma (39) and cholangiocarcinoma (40). Further, MAGEH1 overexpression inhibits proliferation, cell migration, and invasion in hepatocellular carcinoma (39), induces apoptosis in melanoma cell lines (41), and cell cycle arrest in multiple cancer cell lines (40,42). In agreement with these studies, we also observed that MAGEH1 is significantly downregulated with advanced grade of glioma.…”

Section: Discussionsupporting

confidence: 90%

Downregulation of Brain Enriched Type 2 MAGEs Is Associated With Immune Infiltration and Poor Prognosis in Glioma

et al. 2020

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Melanoma associated antigen (MAGE) is an extensively studied family of tumor-associated genes that share a common MAGE homology domain (MHD). Based upon their expression pattern, MAGE genes have been broadly classified into type 1 MAGEs (T1Ms) and type 2 MAGEs (T2Ms) categories. Interestingly, several T2Ms are highly expressed in the brain and involved in the regulation of neuronal development, differentiation, and survival. Available literature suggests possible tumor suppressor functions of a few T2Ms, while information available about their expression, regulation, and clinical significance in glioma is scanty. This prompted us to perform a comprehensive analysis of T2M expression in glioma. Gene expression data from glioma datasets: Oncomine, TCGA, and REMBRANDT study, were used to assess the mRNA expression of T2M genes (MAGED1, MAGED2, MAGED3, MAGED4, MAGED4B, MAGEE1, MAGEE2, MAGEF1, MAGEH1, MAGEL2, NSMCE3, and NDN), and their association with clinical characteristics and composition of the tumor microenvironment. Further, mutation, copy number alteration, and DNA methylation data from TCGA were assessed for determining potential mechanisms of T2Ms expression in glioma. Expression analysis revealed overexpression of MAGED subfamily genes in glioma, while other genes of this family exhibited reduced expression in advanced grades of this malignancy. Further, the expression of T2Ms exhibited varying extent of positive correlations with each other. Amongst downregulated T2Ms, MAGEH1 expression exhibited negative correlations with DNA methylation. Additionally, genes associated with MAGEH1 were enriched in Myc and Hedgehog signaling. Furthermore, T2Ms downregulation was associated with immune infiltration in glioma tissues and poor overall survival of glioma patients. In multivariate Cox regression analysis, MAGEH1 emerged as an independent prognosticator in lower grade glioma. Conclusively, these results suggest that expression of T2Ms is associated with important clinical and molecular features in glioma. Mechanistic studies may further provide novel insights into their role in glioma progression.

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Section: Discussionsupporting

confidence: 90%

Downregulation of Brain Enriched Type 2 MAGEs Is Associated With Immune Infiltration and Poor Prognosis in Glioma

et al. 2020

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“…So, cell cycle arrest, which is associated with inhibition of cell proliferation, is a crucial target of anti-cancer treatment strategy. Down-regulation of cyclin-dependent kinase subunits (CDKs) induced cell cycle arrest and, therefore, could be an important anti-cancer activity [9,10].…”

Section: Introductionmentioning

confidence: 99%

Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

et al. 2016

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Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

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“…Since PRC1 expresses highly in the G2 phase (Fig. 3c ), it regulates elongation and polarity of the spindle 27 , 28 . Thus, its effective downregulation blocks the normal process of elongation and polarization of the spindle, causing G2/M phase arrest.…”

Section: Discussionmentioning

confidence: 99%

Regulation of proliferation and cell cycle by protein regulator of cytokinesis 1 in oral squamous cell carcinoma

Shi

Zhang

et al. 2018

Cell Death Dis

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Protein regulator of cytokinesis 1 (PRC1), a microtubule-associated protein, has emerged as a critical regulator of proliferation and apoptosis, acting predominantly in numerous tumors. However, its function in oral squamous cell carcinoma (OSCC) is still unknown. To establish the roles of PRC1 in OSCC, 95 oral clinical samples (54 OSCC, 24 oral leukoplakia [OLK], and 17 normal oral mucosa) and seven oral cell lines (6 OSCC and 1 normal oral cell lines) were analyzed using a series of molecular and genomic assays both in vivo and in vitro were conducted in this study. Herein, we provide evidence demonstrating that expression of PRC1 closely correlates with the degree of epithelial dysplasia in OLK (n = 24) (p < 0.001), and the poor differentiation, large tumor volume, lymph node metastasis, and high-clinical stage in OSCC (n = 54) (p < 0.05), illustrating that PRC1 has a promotive influence on tumor progression in OSCC. Simultaneously, we observed that PRC1 knockdown in OSCC cell lines caused G2/M phase arrest (p < 0.05), inhibited cell proliferation in vitro (p < 0.05) and tumor growth in vivo (p < 0.001). Furthermore, the effects of PRC1 on the regulation of proliferation and cell cycle transition in OSCC samples were mediated by p53. The p53/PRC1/EGFR signaling pathway was found to be implicated in the tumor progression of OSCC. Based on our data, we demonstrate that PRC1 is a key factor in regulating proliferation and the cell cycle, pointing to the potential benefits of PRC1-targeted therapies for OSCC.

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Apoptosis-related protein-1 acts as a tumor suppressor in cholangiocarcinoma cells by inducing cell cycle arrest via downregulation of cyclin-dependent kinase subunits

Cited by 17 publications

References 39 publications

Downregulation of Brain Enriched Type 2 MAGEs Is Associated With Immune Infiltration and Poor Prognosis in Glioma

Downregulation of Brain Enriched Type 2 MAGEs Is Associated With Immune Infiltration and Poor Prognosis in Glioma

Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

Regulation of proliferation and cell cycle by protein regulator of cytokinesis 1 in oral squamous cell carcinoma

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