Adenovirus-mediated siRNA targeting NOB1 inhibits tumor growth and enhances radiosensitivity of human papillary thyroid carcinoma in vitro and in vivo
Authors: Shuai Xue
Guang Chen
Gui-Min Wang
Wei Meng
Xian-Ying Meng
Pei-Song Wang
Jia Liu
Journal: Oncology Reports (2014)
Discipline: CLINICAL MEDICINE
Keywords: NOB1; papillary thyroid carcinoma; tumor growth; radiosensitivity; cell proliferation
Affiliations: Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

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. 

Retracted: No

PubPeer comments:
 Fig 7C.  Protein samples extracted from TPC1 tumors (n=10 group) were analyzed using western blot analysis for NOB1 expression levels .  Unexpectedly similar to bands from Figs 4C, 5D of [Zhang et al (2014)] ...  ... Fig 5C, [Li et al (2014)] .  And Fig 4 of [Li et al (2015)] .  , 
 Figs 3C, 5.  Western blot analysis of Bcl-2 and XIAP protein expression after infection with Ad sh-Scramble or Ad sh-NOB1. GAPDH was used as an internal control. Each assay was performed at least in triplicate ;  Phosphorylation activation pattern of p38 MAPK, ERK1 2 and JNK was measured by western blotting 24 h after infection with Ad sh-Scramble or Ad sh-NOB1 in the TPC1 cell line .  The bands overlap considerably (with a 180-deg flip in one case) with those of Fig 6 from [Zhang et al (2014)] ,  Effect of CXB and XIAP-shRNA alone or in combination on the PI3K AKT signaling pathway in A549 cells. Phosphorylation activation pattern of PI3K and Akt were measured by western blotting 24 h after treatment with CXB and XIAP-shRNA alone or in combination in the A549 cell line .  The loading control for 5 was identified as beta-Actin in Fig 7 from [Liu et al (2014)] .  ,