Pim-1 kinase is a target of miR-486-5p and eukaryotic translation initiation factor 4E, and plays a critical role in lung cancer

Molecular Cancer

Research

Lingxiao Xing¹  Xin Tian¹  Fan Bai¹  Haitao Shen¹  Wenshuai Pang¹  Ruiyu Han¹  Xia Yan¹  Xianghong Zhang²  Juan Wang³  Yueping Liu⁴  Feng Jiang⁵ 

[1] Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei, China;Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei, China;Department of Pathology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;Department of Pathology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;Department of Pathology, Tumor Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA;

关键词: Epidermal Growth Factor Receptor;    Gefitinib;    NSCLC Cell;    Normal Lung Tissue;    NSCLC Tissue;   

DOI  :  10.1186/1476-4598-13-240

 received in 2014-06-11, accepted in 2014-10-10,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundPim-1 kinase is a proto-oncogene and its dysregulation contributes to tumorigenesis and progression of a variety of malignancies. Pim-1 was suggested as a therapeutic target of cancers. The functional relevance of Pim-1 and the mechanism underlying its dysregulation in lung tumorigenesis remained unclear. This study aimed to investigate if Pim-1 has important functions in non-small-cell lung cancer (NSCLC) by: 1) evaluating the clinicopathologic significance of Pim-1 through analysing its expression in 101 human NSCLCs tissues using quantitative PCR, Western Blot and immunohistochemical studies, 2) determining its role in NSCLC and drug resistance using in vitro assays, and 3) investigating the regulatory mechanism of Pim-1 dysregulation in lung tumorigenesis.ResultsPim-1 was upregulated in 66.2% of the lung tumor tissues and its expression was significantly related to advanced stage (P = 0.019) and lymph node metastasis (P = 0.026). Reduced Pim-1 expression suppressed NSCLC cell growth, cell cycle progression and migration in vitro. Pim-1 was a novel target of miR-486-5p determined by luciferase report assay, and ectopic miR-486-5p expression in cancer cells reduced Pim-1 expression. Furthermore, eukaryotic translation initiation factor 4E (eIF4E) controlled the synthesis of Pim-1 in NSCLC cells, and its expression was positively associated with that of Pim-1 in NSCLC tissue specimens (r = 0.504, p < 0.001). The downregulated miR-486-5p and upregulated eIF4E in NSCLC cells led to the overexpression of Pim-1 by relieving the inhibitory effect of the 3′-UTR or 5′-UTR of Pim-1 mRNA, respectively. Moreover, Pim-1 knockdown sensitized NSCLC cells to cisplatin and EGFR tyrosine kinase inhibitor, gefitinib.ConclusionsPim-1 kinase could be a critical survival signaling factor in NSCLC, and regulated by miR-486-5p and eIF4E. Pim-1 kinase may provide a potential target for diagnosis and treatment for lung cancer.

【 授权许可】

Unknown   
© Pang et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.