Interaction mechanism between four transmembrane protein 1 and JAK2-STAT3 signaling pathway in lung cancer cells and analysis of its expression in non-small cell lung cancer

Abstract:

Objective：To investigate the expression of four transmembrane protein 1（TM4SF1） in non-small cell lung cancer（NSCLC） and its relationship with clinicopathological features in NSCLC patients，to construct TM4SF1 lentiviral expression vector for stably transfecting lung cancer A549 cells，and to investigate the mechanism of interaction between TM4SF1 and JAK2-STAT3 signaling pathway in lung cancer cells. Methods：Resected cancer tissue and corresponding adjacent paracarcinoma of 61 patients with NSCLC and resected benign lung tissue of 10 patients were collected. Real-time immunofluorescence quantitative PCR（qRT-PCR） and Western blot were used to detect the expression of TM4SF1 in NSCLC tissues，paracancerous tissues and normal lung tissues. Lentiviral transfection was used to detect highly expressed TM4SF1 gene in lung cancer A549 cells. The qRT-PCR and Western blot were used to analyze the expression level of TM4SF1 gene and Sox2 gene. Transwell was used to examine the effect of high-expression TM4SF1 on A549 migration. Results：The expression of TM4SF1 mRNA and its protein in cancer tissues was significantly higher than that in adjacent tissues（P<0.05） and in normal lung tissues（P<0.05）；TM4SF1 expression was not associated with age and gender，but was associated with tumor size，degree of differentiation，lymph node metastasis，and clinical stage（P<0.05）. High-expressing TM4SF1 in lung cancer A549 cell line was successfully constructed，which was able to significantly enhance the migration ability of A549 cells and up-regulate the expression level of Sox2 in the downstream of AK2-STAT3 signaling pathway. Conclusion：TM4SF1 is highly expressed in NSCLC and overexpression of this gene can promote the migration of A549 cells and up-regulate the expression level of Sox2 in the downstream of JAK2-STAT3 signaling pathway. TM4SF1 may promote the development and distant metastasis of NSCLC through this pathway，and TM4SF1 may become a potential therapeutic target for NSCLC.