Downregulation of NOB1 suppresses the proliferation and tumor growth of non-small cell lung cancer in vitro and in vivo.
Non-small cell lung cancer (NSCLC) is a lethal disease due to the absence of effective diagnostic biomarkers and therapeutic targets. Therefore, novel molecular targets are critically needed to formulate new approaches for this devastating disease. In the present study, using quantitive real-time PCR and immunohistochemistry. we initially found that expression of the ribosome assembly factor NIN/RPN12 binding protein (NOB1) was elevated in the majority of NSCLC tissues when compared to that in the normal lung tissue counterparts, and its expression level was correlated with key pathological characteristics including tumor differentiation, stage and metastasis. Then, the recombinant lentiviral shRNA expression vector carrying NOB1 was constructed and infected into the human NSCLC A549 cell line. Cell proliferation, cell apoptosis, cell cycle distribution and colony formation ability in A549 cells were assessed following downregulation of NOB1 by siRNA. In addition, tumor growth ability in nude mice was evaluated to define the function of NOB1 in cell transformation and tumorigenesis. It was found that downregulation of NOB1 expression using the RNA silencing approach in A549 tumor cells significantly suppressed the proliferation and colony formation ability, and induced tumor apoptosis in vitro. Tumor growth was also suppressed in vivo. These data suggest that NOB1 is an important regulator of the tumorigenic properties of human NSCLC and may be used as a new promising diagnostic biomarker and a potential anticancer therapeutic target for NSCLC.
Department of Respiration, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Yang
Y
Li
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Chengyuan
C
Ma
Prosthodontics Department of the Stomatological Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.
Ming
M
Qian
Department of Respiration, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Zhongmei
Z
Wen
Department of Respiration, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Hongyu
H
Jing
Department of Respiration, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Donghua
D
Qian
D000818:Animals; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D056743:Cyclin D3 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C530104:CCND1 protein, human; C534696:CCND3 protein, human; D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21; C506664:NOB1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D019938:Cyclin D1