title: Thoc1 inhibits cell growth via induction of cell cycle arrest and apoptosis in lung cancer cells.
abstract: THO complex 1 (Thoc1) is a human nuclear matrix protein that binds to the retinoblastoma tumor suppressor retinoblastoma protein (pRb). While some studies suggest that Thoc1 has characteristics of a tumor suppressor protein, whether Thoc1 can inhibit lung cancer cell growth is not clear. In the present study, we observed that Thoc1 is lowly expressed in the lung cancer cell lines SPC-A1 and NCI-H1975. Then, we investigated the potential effects of Thoc1 on lung cancer cell proliferation, cell cycle and apoptosis after stable transfection of these lines with a Thoc1 expression vector. We found that overexpression of Thoc1 can inhibit cell proliferation, induce G2/M cell cycle arrest and promote apoptosis. Further investigation indicated that overexpression of Thoc1 is involved in the inhibition of cell cycle-related proteins cyclin A1 and B1 and of pro-apoptotic factors Bax and caspase-3. In vivo experiments showed that tumors overexpressing Thoc1 display a slower growth rate than the control xenografts and show reduced expression of the protein Ki-67, which localized on the nuclear membrane. Taken together, our data show that in lung cancer cells, Thoc1 inhibits cell growth through induction of cell cycle arrest and apoptosis. These results indicate that Thoc1 may be used as a novel therapeutic target for human lung cancer treatment.
authors.affiliation: School of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wan
authors.affiliation: Oncology Institute, Wuxi Fourth People's Hospital, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Shitao
authors.initials: S
authors.lastname: Zou
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Mengshang
authors.initials: M
authors.lastname: Hu
authors.affiliation: School of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhu
authors.affiliation: School of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: School of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Saijun
authors.initials: S
authors.lastname: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D047368:Tumor Burden; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016601:RNA-Binding Proteins; C400546:THOC1 protein, human; D051028:bcl-2-Associated X Protein; D053148:Caspase 3