Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MCPH1, initially identified as an hTERT repressor, has recently been implicated in mediating DNA damage response and maintaining chromosome integrity. This study is to investigate its potential role in the onset of cervical cancer. In the study, decreased expression of MCPH1 was observed in 19 of 31 cases (61.3%) at mRNA level and 44 of 63 cases (69.8%) at protein level of cervical tumor tissues compared with the paired nontumor tissues. Reduced MCPH1 protein expression was significantly associated with high-tumor grade (1 vs. 3 P = 0.013; 2 vs. 3 P = 0.047). In addition to inhibit SiHa cell migration and invasion, the overexpression of MCPH1 inhibited cervical cancer cells growth through inducing S phase arrest and mitochondrial apoptosis. Further analysis demonstrated cyclinA2/CDK2, CDC25C-cyclinB/CDC2, and p53/p21 pathways were involved in the MCPH1 overexpression-induced S phase arrest. Moreover, the overexpression of MCPH1 activated mitochondrial apoptosis through regulating several apoptosis-related proteins such as p53, Bcl-2, Bax, cytochrome c, caspase-3, and PARP-1. Our findings indicate that downregulated MCPH1 correlates with tumor progression in cervical cancer, and MCPH1 has an important role in regulating cell growth through regulating the cell cycle and apoptosis. Thus, it may be a crucial tumor suppressor gene and a novel candidate therapeutic target for cervical cancer.
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PMID:The overexpression of MCPH1 inhibits cell growth through regulating cell cycle-related proteins and activating cytochrome c-caspase 3 signaling in cervical cancer. 2463 62

Cancer predisposition genes (CPGs) are a class of cancer genes in which germline variants lead to increased risk of cancer. Research has revealed that copy number variation (CNV) may be linked to cancer susceptibility in CPGs. In this pan-cancer analysis, we explored the relationship between somatic CNV and gene expression changes in CPGs. Based on curated 827 human CPGs from literature, we firstly identified 729 CPGs with precise CNV information from 5067 tumor samples using TCGA CNV data. Among them, 128 CPGs tended to have more frequent copy number losses (CNLs) compared with copy number gains (CNGs). Then by correlating these CNV data with TCGA gene expression data, we obtained 49 CPGs with concordant CNLs and gene down-regulation. Intriguingly, five CPGs showed concordance between CNL and down-regulation in 50 or more tumor samples: MTAP (216 samples), PTEN (143), MCPH1 (86), SMAD4 (63), and MINPP1 (51), which may represent the recurrent driving force for gene expression change during oncogenesis. Moreover, network analysis revealed that these 49 CPGs were tightly connected. In summary, this study provides the first observation of concordance between CNLs and down-regulation of CPGs in pan-cancer, which may help better understand the CPG biology in tumorigenesis and cancer progression.
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PMID:Concordance between somatic copy number loss and down-regulated expression: A pan-cancer study of cancer predisposition genes. 2792 28