Long non-coding RNA FTH1P3 promotes the metastasis and aggressiveness of non-small cell lung carcinoma by inducing epithelial-mesenchymal transition

长链非编码RNA FTH1P3通过诱导上皮间质转化促进非小细胞肺癌的转移和侵袭性

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作者:Zhengxiong Li, Yadi Wang

Abstract

Long non-coding RNAs (lncRNAs) ferritin heavy chain 1 pseudogene 3 (FTH1P3) has been suggested to act as an oncogene in many types of human malignancy, but its role in non-small cell lung carcinoma (NSCLC) remains unknown. This study aimed to characterize the biologic functions of FTH1P3 in NSCLC and illuminate its clinical significance. The expression levels of FTH1P3 in NSCLC tissues and cell lines were detected by quantitative real-time PCR assay. The relationship of FTH1P3 expression with clinicopathologic features was evaluated by chi-square test, and its correlation with prognosis of NSCLC patients was analyzed by Kaplan-Meier method with log-rank test. Wound healing and transwell invasion assays were applied to evaluate cell migration and invasion abilities, respectively. Western blotwas performed to detect the changes of epithelial-mesenchymal transition (EMT) related protein expression. The results showed that FTH1P3 was highly expressed in NSCLC tumor tissues and NSCLC-derived cell lines, and high expression of FTH1P3 was associated with advanced TNM stage and lymph node metastasis. NSCLC patients with high FTH1P3 expression had a poor overall survival relative to patients with low FTH1P3 expression. Through loss-of-function studies, FTH1P3 inhibition was demonstrated to suppress NSCLC cell migration and invasion in vitro. Notably, FTH1P3 knockdown could decrease expression of N-cadherin, vimentin and Snail protein of NSCLC cells, but promote E-cadherin protein expression, which was in accordance with its effect on cell migration and invasion. To sum up, our data demonstrated that FTH1P3 predicts a poor prognosis and promotes metastasis and aggressiveness in NSCLC by inducing EMT, suggesting FTH1P3 may be a promising target for gene therapy of NSCLC.

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