Abstract 1836: Long noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free interval in human non-small cell lung cancer.

Abstract

Abstract Lung cancer is the most common cause of cancer death worldwide. Non- small cell lung cancer (NSCLC) occupies more than 80% of all lung cancer. Overall, less than 10% of patients diagnosed with NSCLC survive five years after the diagnosis. Multidisciplinary management of NSCLC which contains surgery, chemotherapy and radiotherapy does not satisfactorily improve the patients’ prognosis. The pathogenic mechanisms contributing to the resistance to various therapeutic approaches in this cancer still remain to be clarified. HOTAIR is one of the large intervening noncoding RNA and interacts with the polycomb repressive complex 2 (PRC2) in the regulation of gene activities. Recently, the enhanced expression of this molecule has been shown to be associated with metastasis and/or poor prognosis of several human carcinomas such as breast, liver, colon and pancreas. However, little is known about the roles of this gene in lung cancer. Thus, we examined the involvement of HOTAIR in the development of NSCLCs. The expression of HOTAIR was examined in 77 NSCLCs and their corresponding normal lung tissues, and 6 metastatic lesions to brain by quantitative real-time RT-PCR. The high expression of HOTAIR (tumor/normal ratio > 2) was detected in 17 patients (22.1%) and was frequently found in patients with advanced stage, lymph node metastasis or lymphovascular invasion. The NSCLC patients with high expression of HOTAIR also showed significantly short disease free interval compared with those with low expression. Furthermore the metastatic lesions to brain demonstrated significantly higher HOTAIR expression than primary tissues. Accordingly, HOTAIR transfected A549 cells showed induced migration in vitro, and injected HOTAIR expressing cells into the tail vein of immunodeficient mice formed more metastases to liver or bone compared to empty vector transfected cells. We also found that the enhanced HOTAIR expression in lung cancer cells demonstrated the reduced expression of LAMB2 and LAMC3 both of which are downstream targets of PRC2. Taken together, these results might indicate that the evaluation of HOTAIR expression predict the poor outcome of NSCLC patients and that the overexpression of HOTAIR enhanced the aggressive biological behavior of NSCLC cells, at least in part, through the regulation of PRC2. Citation Format: Takayuki Nakagawa. Long noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free interval in human non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1836. doi:10.1158/1538-7445.AM2013-1836