Expression of lncRNA DLEU1 in non-small cell lung cancer and its effect on metastasis / 中国肿瘤临床

ABSTRACT

Objective: To investigate the expression pattern and clinical significance of long non-coding RNA deleted in lymphocytic leu-kemia 1 (DLEU1) in non-small cell lung cancer (NSCLC), and to further evaluate its effect on tumor metastasis. Methods: Paired cancer and adjacent tissues were obtained from 42 patients with NSCLC that underwent surgical resection of cancer in The Third Xiangya Hos-pital of Central South University from January 2008 to December 2012, at the Department of Cardiothoracic Surgery. The expression features of DLEU1 in NSCLC tissue were detected by real-time quantitative polymerase chain reaction assay. Statistical methods were used to analyze the relationship between the expression of DLEU1 and the clinicopathological features and the survival time of pa-tients with NSCLC. Effects of DLEU1 on migration and invasion of NSCLC cells were evaluated by in vitro wound healing and cell inva-sion assays, respectively. Western blot was performed to investigate the protein levels of E-cadherin, N-cadherin, and Vimentin, which are the biomarkers of epithelial to mesenchymal transition (EMT). Results: Of the 42 NSCLC samples, DLEU1 expression was up-regulat-ed in 35 samples (83.33%) and down-regulated in 7 samples (16.67%). The expression level of DLEU1 in NSCLC tissue was 2.11 times that in the adjacent tissues (P<0.05). The expression of DLEU1 in four NSCLC cell lines (A549, H1299, SPCA1, and H358) was higher than that in normal lung 16HBE epithelial cells, and of these, A549 cells had the highest DLEU1 expression (P<0.05). Highly expressed DLEU1 was positively correlated with lymph-node metastasis (P<0.05), but was not significantly associated with other parameters, in-cluding patient gender, age, smoking history, primary tumor size, histological grade, and the TNM stage. The survival time of patients with high DLEU1 expression was significantly shorter than that of patients with low DLEU1 expression (P<0.05). In vitro interference with DLEU1 expression significantly inhibited the migration and invasion of A549 and SPCA1 cells compared with that of the control group (P<0.05). Upon interference with DLEU1 expression , protein levels of E-cadherin increased, whereas those of N-cadherin and Vi-mentin decreased in A549 cells in comparison with the control group. Conclusions: The expression of DLEU1 is up-regulated in NSCLC tissues and cell lines, correlates with lymph-node metastasis and survival times in patients with NSCLC, and promotes tumor cell migra-tion and invasion by regulating EMT, suggesting that DLEU1 may be a potential therapeutic target for NSCLC.