Oncotarget

Research Papers:

KLF15 promotes the proliferation and metastasis of lung adenocarcinoma cells and has potential as a cancer prognostic marker

Lihua Gao, Hongmei Qiu, Jian Liu, Yuzhen Ma, Jia Feng, Li Qian, Jianguo Zhang, Yifei Liu _ and Tingting Bian

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Oncotarget. 2017; 8:109952-109961. https://doi.org/10.18632/oncotarget.21972

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Abstract

Lihua Gao1,*, Hongmei Qiu2,*, Jian Liu1, Yuzhen Ma3, Jia Feng4, Li Qian4, Jianguo Zhang4, Yifei Liu4 and Tingting Bian4

1Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China

2Department of Respiration, Nantong Geriatric Rehabilitation Hospital, Branch of Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China

3Centre of Reproductive Medicine, Inner Mongolia Hospital, Inner Mongolia, Hohhot, 010021, China

4Department of Pathology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China

*These authors contributed equally to this work

Correspondence to:

Yifei Liu, email: ntdxliuyifei@sina.com

Tingting Bian, email: ntdxbiantingting@sina.com

Keywords: KLF15, lung adenocarcinoma, cell proliferation, cell migration, prognosis

Received: March 27, 2017     Accepted: September 24, 2017     Published: October 19, 2017

ABSTRACT

Lung adenocarcinoma (LADC)is a general form of non-small cell lung cancer that represents a significant threat to public health worldwide. The 5-year-survival rate for LADC is currently below 15%. The transcription factor KLF15, also called kidney-enriched KLF (KKLF), has been proven to play a role in inhibiting proliferation and diversification of carcinoma cells, including those of the endometrium, pancreas and breast, but the involvement of KLF15 in LADC has not previously been studied. In this study, we compared the in vitro expression of KLF15 in human LADC tissues and adjacent normal lung tissues. Expression of KLF15 was found to be abnormally high in LADC tissues and cells compared with adjacent non-tumorous tissues, and was correlated with tumor TNM stage and tumor differentiation (P = 0.003, P = 0.001, respectively). The effect of KLF15 on cell growth and migration were explored in vitro by Western Blotting, CCK8 and colony formation assays, flow cytometry analysis and transwell migration assays, and in vivo by analysis of tumorigenesis in 5-week old BALB/c nude mice. Knockdown of KLF15 significantly upregulated the protein levels of cleaved caspase-3, caspase-7, caspase-8 and PARP, thereby inducing apoptosis. Downregulation of KLF15 in A549 and NCI-H1650 cell lines resulted in these cell lines exhibiting markedly slower growth rates when injected subcutaneously into the flank of nude mice, compared with the comparator control groups (P < 0.05). Collectively, our findings suggest that KLF15 may have a significant effect on LADC cell survival, and that it represents a potential therapeutic and preventive biomarker for LADC prognosis and treatment.


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