The Expression of RNA-Binding Protein HuR in Non-Small Cell Lung Cancer Correlates with Vascular Endothelial Growth Factor-C Expression and Lymph Node Metastasis

• Published in: Oncology Vol. 76; no. 6; pp. 420 - 429
• Main Authors: Wang, Jun, Zhao, Weipeng, Guo, Yan, Zhang, Bicheng, Xie, Qichao, Xiang, Debing, Gao, Jianfei, Wang, Baocheng, Chen, Zhengtang
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2009; S. Karger AG
• Subjects: Adenocarcinoma - metabolism; Aged; Antigens, Surface - biosynthesis; Biological and medical sciences; Biomarkers; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - metabolism; Clinical Translational Research; ELAV Proteins; ELAV-Like Protein 1; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lung cancer; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lymphatic Metastasis; Male; Medical sciences; Metastasis; Microscopy, Confocal; Middle Aged; Oncology; Pneumology; RNA-Binding Proteins - biosynthesis; RNA-Binding Proteins - chemistry; Tumors; Tumors of the respiratory system and mediastinum; Vascular Endothelial Growth Factor C - biosynthesis; Vascular endothelial growth factor-C; HuR; Non-small cell lung cancer; mRNA stability; Lung disease; Stability; Respiratory disease; Lung cancer; RNA binding protein; Malignant lymphadenopathy; Malignant hemopathy; Malignant tumor; non-small cell lung carcinoma; Lymph node metastasis; Cancerology; Messenger RNA; Vascular endothelial growth factor C; Bronchus disease; Cancer
• ISSN: 0030-2414; 1423-0232
• DOI: 10.1159/000216837

The expression levels of the RNA-binding protein Hu antigen (HuR) and vascular endothelial growth factor-C (VEGF-C) were examined immunohistochemically in 81 non-small cell lung cancers (NSCLC) and 15 benign human lung tissues. HuR showed a nuclear overexpression in 82.7% (67/81) of NSCLC specimens. Cytoplasmic immunoreactivity for HuR was observed in 45.7% (37/81) of NSCLC, while only nuclear expression of HuR was observed in 13.3% (2/15) of benign lung tissues. The expression of VEGF-C was present in a subgroup of 70.4% (57/81) of tumor cases. In the human NSCLC samples, cytoplasmic but not nuclear HuR expression was significantly associated with increased levels of VEGF-C and with clinicopathological variables, including high tumor grade, poor differentiation and lymph node metastasis. In vitro, HuR showed a predominantly nuclear staining in Lewis lung cancer cells, as seen by confocal microscopy. When lung cancer cells were treated with siRNA targeted against HuR, expression levels of the HuR and VEGF-C proteins were significantly reduced, as seen by Western blotting. Our findings indicate that there is a dysregulation of the cellular distribution of the mRNA stability factor HuR in a subset of NSCLC. Examination of cytoplasmic HuR in NSCLC tissues will allow for valuable prognostic diagnosis of lymph node metastasis, as HuR might be an important mediator regulating the expression of VEGF-C.