The Role of Neurotrophin-4/Forkhead Box L1 in the Development of Nonsmall-Cell Lung Cancer.

Abstract

This study aims to uncover the biological function of neurotrophin-4 (NTF4) in affecting the progression of nonsmall-cell lung cancer (NSCLC). NTF4 levels in NSCLC and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Knockdown of NTF4 in A549 and H1299 cells was achieved by transfection of sh-NTF4. Subsequently, proliferative and migratory changes in NSCLC cells with NTF4 knockdown were determined by cell counting kit-8 (CCK-8) and transwell and wound healing assay. The target gene binding NTF4 was predicted by bioinformatic software and verified by a dual-luciferase reporter assay. The role of the NTF4/FOXL1 axis in mediating NSCLC cell behaviors was finally explored through rescue experiments. NTF4 was highly expressed in NSCLC tissues than in normal ones. Knockdown of NTF4 remarkably reduced proliferative and migratory rates in A549 and H1299 cells. Forkhead Box L1 (FOXL1) was confirmed as a target gene of NTF4 by bioinformatic software and verified by a dual-luciferase reporter assay. Knockdown of FOXL1 was able to reverse the reduced proliferative and migratory rates in A549 and H1299 cells transfected with sh-NTF4. NTF4 triggers NSCLC to proliferate and migrate via negatively regulating FOXL1.