title: The overexpression of MCPH1 inhibits cell growth through regulating cell cycle-related proteins and activating cytochrome c-caspase 3 signaling in cervical cancer.
abstract: 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.
authors.affiliation: Department of Biochemistry & Molecular Biology, Molecular Medicine & Cancer Research Center, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Mai
authors.forename: Faping
authors.initials: F
authors.lastname: Yi
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gou
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Changdong
authors.initials: C
authors.lastname: Wang
authors.forename: Geli
authors.initials: G
authors.lastname: Liu
authors.forename: Youquan
authors.initials: Y
authors.lastname: Bu
authors.forename: Chengfu
authors.initials: C
authors.lastname: Yuan
authors.forename: Linman
authors.initials: L
authors.lastname: Deng
authors.forename: Fangzhou
authors.initials: F
authors.lastname: Song
mesh_terms: D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D005260:Female; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D017931:DNA Primers; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins; D045304:Cytochromes c; D053148:Caspase 3