Long noncoding RNA FER1L4 suppresses proliferation, invasion, migration and lymphatic metastasis of gastric cancer cells through inhibiting the Hippo-YAP signaling pathway

摘要

Gastric cancer (GC) is one of the most malignant tumors in the world. Growing evidence has highlighted the crucial role of long noncoding RNAs (lncRNAs) in the tumorigenesis of GC. The aim of the research was to elucidate the effects of lncRNA Fer-1-like family member 4 (FER1L4) in GC and identify the potential mechanisms. The present study investigated FER1L4 controlling cell survival and migration of SGC-7901 cells. Results indicated that the expression level of FER1L4 was distinctly decreased in GC cells, as evidenced by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. By using cell proliferation assay, Transwell assay, wound healing assay and western blotting, we found out that overexpression of FER1L4 in SGC-7901 cells hindered the capacities of cell proliferation, invasion, migration and lymphatic metastasis. Furthermore, results of the western blotting and immunofluorescence assay unveiled that overexpression of FER1L4 led to a notable reduction in the expression of C-X-C chemokine receptor type 4 (CXCR4) and C-X-C motif chemokine 12 (CXCL12) in SGC-7901 cells. Besides, activation of Hippo pathway by upregulating Yes-associated protein (YAP) expression or treatment of CXCR4 inhibitor WZ811 reversed the inhibitory effects of FER1L4 on proliferation and metastasis of SGC-7901 cells. Moreover, co-transfection with YAP and FER1L4 overexpression plasmids abrogated the repressive effects of FER1L4 overexpression on proliferation and metastasis. Taken together, these results demonstrated that lncRNA FER1L4 suppressed cell proliferation, invasion, migration and lymphatic metastasis of GC cells by inactivation of the Hippo-YAP pathway, providing novel insights into regulatory mechanism under GC and new strategies for clinical practice.