Objective: The aim of this study was to investigate the effect of long non-coding RNA (lncRNA) WT-AS on the invasiveness and migration of non-small cell lung cancer (NSCLC) cells, and to explore the underlying molecular mechanism of lncRNA WT-AS in the pathogenesis of NSCLC.
Patients and methods: LncRNA WT-AS expression in 50 pairs of NSCLC tissues and adjacent ones was studied by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and the correlations of WT-AS with clinicopathological indicators and prognosis of NSCLC patients were analyzed. Meanwhile, NSCLC expression levels in NSCLC cell lines were also evaluated by qPCR assay. In addition, WT-AS overexpression and knockdown models were constructed using lentivirus in NSCLC cell lines A549 and H1299, respectively. Thereafter, transwell and cell wound healing assays were carried out to assess the implication of WT-AS in biological functions of NSCLC cells. Furthermore, the interaction between WT-AS and KLK13 was determined via Luciferase assay.
Results: The results showed that WT-AS expression in NSCLC was remarkably lower than that in normal tissues adjacent to the cancer. Univariate analysis suggested that compared with patients with high expression of WT-AS, patients in low expression group showed higher incidence of metastasis and lower survival rates. Overexpression of WT-AS suppressed cell invasion and metastasis capacity, while the opposite result was observed in WT-AS knockdown group. KLK13 expression showed an increase in NSCLC cell lines and tissues, which was negatively correlated with WT-AS level. Meanwhile, Luciferase assay confirmed the binding between WT-AS and KLK13. Western blotting revealed that KLK13 expression was remarkably elevated in EC tissues and was positively correlated with TRIM62. In addition, it was also found that WT-AS and KLK13 had a mutual regulatory effect, which together affect the malignant progress of NSCLC.
Conclusions: This study shows for the first time that LncRNA WT-AS interacts with KLK13 to serve as a negative regulator of NSCLC progression.