Overexpression of RNF146 in non-small cell lung cancer enhances proliferation and invasion of tumors through the Wnt/β-catenin signaling pathway.
Studies have suggested a possible correlation between the newly identified E3 ubiquitin ligase ring finger protein 146 (RNF146) and tumor development. However, until now, studies on RNF146 have been restricted to poly(ADP-ribosyl)ation and ubiquitin ligation, whereas the role of RNF146 in tumor biology has rarely been reported. In the present study, the role of RNF146 in non-small cell lung cancer (NSCLC) was investigated. The results showed that the expression of RNF146 was increased in clinical lung cancer samples and cell lines. RNF146 expression correlated with tumor size, differentiation level, lymphatic metastasis, pTNM staging, and prognosis of patients in stage I. RNF146 expression was negatively correlated with Axin expression but positively correlated with the nuclear expression of β-catenin in NSCLC tissues. RNF146 downregulated the expression of Axin in lung cancer cell lines and induced the expression and nuclear distribution of β-catenin. Overexpression of RNF146 in NSCLC cell lines increased the levels of cyclinD1, cyclinE, and CDK4, promoted cell cycle G0/G1-S transitions, and regulated cell proliferation. Overexpression of RNF146 led to upregulated levels of matrix metalloproteinases 2 and 7 and enhanced lung cancer cell invasiveness, events that were mediated by the classical Wnt/β-catenin signaling pathway. In summary, the data in the present study indicate that RNF146 regulated the development and progression of NSCLC by enhancing cell growth, invasion, and survival, suggesting that RNF146 may be a potential treatment target in NSCLC.
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning, China ; Department of Pathology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Ying
Y
Gao
Department of Thoracic Surgery,The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Chengyang
C
Song
Laboratory Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Linping
L
Hui
Department of Thoracic Surgery,The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Chun-yu
CY
Li
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning, China.
Junying
J
Wang
Department of Thoracic Surgery,The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Ye
Y
Tian
Department of Thoracic Surgery,The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Xu
X
Han
Department of Thoracic Surgery,The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Yong
Y
Chen
Department of Thoracic Surgery,The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Da-Li
DL
Tian
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning, China.
Xueshan
X
Qiu
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning, China.
Enhua
E
Wang
D021581:Active Transport, Cell Nucleus; D060466:Axin Protein / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway
D060466:Axin Protein; D019938:Cyclin D1; C561932:RNF146 protein, human; D044767:Ubiquitin-Protein Ligases; D020783:Matrix Metalloproteinase 7