Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 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

Microcephalin (MCPH1/BRIT1) is a large nuclear protein that is involved in the early cellular response to DNA damage, the expression of which is reduced in a variety of types of human tumors. A recent study by our group demonstrated that MCPH1 expression is markedly decreased in lung cancer. However, it remains unclear whether inducing the expression of MCPH1 may ameliorate lung cancer, and, if so, which mechanisms underlie this process. The results of the present study demonstrated that MCPH1 expression was downregulated in lung cancer tissues compared with that in normal lung tissues. Furthermore, MCPH1 overexpression in A549 non-small cell lung carcinoma cells, successfully inhibited cell proliferation via arrest of the cell cycle in the S and G2/M phases. In addition, MCPH1 overexpression promoted cell apoptosis, in association with a significant increase in the quantities of Bax and active caspase-3, as well as a decrease in the level of Bcl-2. In conclusion the present results indicated that MCPH1 is involved in the regulation of apoptosis and entry into mitosis, suggesting that MCPH1 may function as a tumor suppressor and that it may be important in the pathogenesis of lung cancer.
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PMID:Overexpression of MCPH1 inhibits uncontrolled cell growth by promoting cell apoptosis and arresting the cell cycle in S and G2/M phase in lung cancer cells. 2687 Feb 19