title: Adenovirus-mediated siRNA targeting NOB1 inhibits tumor growth and enhances radiosensitivity of human papillary thyroid carcinoma in vitro and in vivo.
abstract: NIN1/RPN12 binding protein 1 homolog (NOB1), a ribosome assembly factor, plays critical roles in tumor progression and development. Previously, we reported that overexpression of NOB1 is correlated with the prognosis of patients with papillary thyroid carcinoma (PTC). Little is known, however, concerning its role in PTC. The aims of the present study were to investigate the association of NOB1 expression with tumor growth and radiosensitivity of human PTC. A recombinant adenovirus expression vector carrying NOB1 was constructed and then infected into the human PTC cell line TPC-1. Cell proliferation, cell cycle distribution, apoptosis, migration and invasion in vitro and tumor growth in vivo were determined after downregulation of NOB1 by RNAi. Additionally, the in vitro and in vivo radiosensitivity of PTC cells was determined by clonogenic cell survival assay and a mouse xenograft model, respectively. The results showed that downregulation of NOB1 expression using RNAi in TPC-1 cells significantly inhibited cell proliferation, migration and invasion and induced cell apoptosis in vitro, and suppressed tumor growth in vivo, as well as enhanced the in vitro and in vivo radiosensitivity of PTC cells. Moreover, our results also showed that downregulation of NOB1 was able to significantly activate constitutive phosphorylation of p38 MAPK, which might contribute to the inhibition of PTC cell growth. These findings suggest that NOB1 may be a potential therapeutic target for the treatment of PTC.
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Pei-Song
authors.initials: PS
authors.lastname: Wang
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Xue
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Gui-Min
authors.initials: GM
authors.lastname: Wang
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xian-Ying
authors.initials: XY
authors.lastname: Meng
authors.affiliation: Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D005260:Female; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C506664:NOB1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D048051:p38 Mitogen-Activated Protein Kinases