Proliferating cell nuclear antigen promotes cell proliferation and tumorigenesis by up-regulating STAT3 in non-small cell lung cancer
Authors: Bing Liu
Weixiang Kong
Xueqing Zhang
Liuxin Wang
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: NSCLC; PCNA; Proliferation; STAT3; Tumorigenesis.
Affiliations: Department of Respiration, Jining First People's Hospital, Jining, Shandong, China., Department of Respiration, Jining First People's Hospital, Jining, Shandong, China. Electronic address: .

Abstract:  Proliferating cell nuclear antigen (PCNA) functions as a bridging molecule, which targets proteins that have distinct roles in cell growth. The expression of PCNA is dysregulated in some tumors and takes part in the progression of oncogenesis. However, the roles of PCNA in the progression of non-small cell lung cancer (NSCLC) remain unknown. The present study aimed to investigate the function of PCNA in the occurrence and development of NSCLC and its underlying molecular mechanisms. Western blotting, RT-PCR, and immunohistochemistry assays were used to detect the expression pattern of PCNA in NSCLC tissues and cells. A log rank test was performed to compare the overall survival (OS) of patients with high/low expression of PCNA. Besides, the relationship between PCNA and signal transducer and activator of transcription-3 (STAT3) proteins were evaluated. Then, MTT, flow cytometry, clonal formation, and in vivo xenograft assays were conducted to investigate the effects of PCNA/STAT3 on cell growth, clonal formation, apoptosis, and tumorigenesis. Results showed that PCNA expression was elevated in NSCLC tissues and cells and it could combine with STAT3 and increased its expression and phosphorylation. Moreover, the expression of PCNA showed a positive correlation with the TNM grade and occurrence rate of the lymphatic metastasis and poor prognosis of NSCLC patients. Overexpression of PCNA promoted cell proliferation, clonal formation, and tumorigenesis in lung cancer cells and inhibited cell apoptosis. In contrast, these effects were inhibited when knockdown of STAT3. In conclusion, this study demonstrates that PCNA functions as an oncogene in the progression of NSCLC through up-regulation of STAT3. These findings point to a potentially new therapeutic strategy for NSCLC. 

Retracted: No

PubPeer comments:
 It does not appear that the authors have decided entirely on what is what in this article: Figure 1D: A micrograph has been duplicated. Figure 2E: An image has been duplicated and presented as something else. Figure 2F: One flow cytometry dot plot is shown three time, and presented as something else. Figure 5H: Two flow cytometry dot plots are identical, but they represent two different treatments. These two dot plots are also seen in Figure 2F. ![file] , 
 It does not appear that the authors have decided entirely on what is what in this article: Figure 1D: A micrograph has been duplicated. Figure 2E: An image has been duplicated and presented as something else. Figure 2F: One flow cytometry dot plot is shown three time, and presented as something else. Figure 5H: Two flow cytometry dot plots are identical, but they represent two different treatments. These two dot plots are also seen in Figure 2F. ![file] ,