title: Overexpression of nuclear apoptosis-inducing factor 1 altered the proteomic profile of human gastric cancer cell MKN45 and induced cell cycle arrest at G1/S phase.
abstract: Nuclear apoptosis-inducing factor 1 (NAIF1) was previously reported to induce apoptosis. Moreover, the expression of NAIF1 was significantly down-regulated in human gastric cancer tissues compared to adjacent normal tissues. However, the mechanism by which the NAIF1 gene induces apoptosis is not fully understood. Our results show that NAIF1 was minimally expressed in all the tested gastric cancer cell lines. Our data also demonstrates that NAIF1 is localized in the nuclei of cells as detected by monitoring the green fluorescence of NAIF1-GFP fusion protein using fluorescent confocal microscopy. Next, a comparative proteomic approach was used to identify the differential expression of proteins between gastric cancer cell lines MKN45/NAIF1 (-) and MKN45/NAIF1 (+). We found five proteins (proteasome 26S subunit 2, proteasome 26S subunit 13, NADH dehydrogenase Fe-S protein 1, chaperonin containing TCP1 subunit 3 and thioredoxin reductase 1) that were up-regulated and three proteins (ribonuclease inhibitor 1, 14-3-3 protein epsilon isoform and apolipoprotein A-I binding protein) that were down-regulated in the MKN45 cells overexpressing NAIF1. We also discovered that NAIF1 could induce cell cycle arrest at G1/S phase by altering the expression of cell cycle proteins cyclinD1, cdc2 and p21. The differentially expressed proteins identified here are related to various cellular programs involving cell cycle, apoptosis, and signal transduction regulation and suggest that NAIF1 may be a tumor suppressor in gastric cancer. Our research provides evidence that elucidates the role of how NAIF1 functions in gastric cancer.
authors.affiliation: Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Jialing
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Abdomen Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing, P.R. China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Sang
authors.affiliation: Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Changzhi
authors.initials: C
authors.lastname: Huang
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055442:Metabolome; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D040901:Proteomics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; C511414:NAIF1 protein, human; D009687:Nuclear Proteins; D020543:Proteome