miR‐107 regulates growth and metastasis of gastric cancer cells via activation of the PI3K‐AKT signaling pathway by down‐regulating FAT4

• Main Authors: Li Wang, Kunkun Li, Chen Wang, Xiaoxin Shi, Huiyu Yang
• Format: Article
• Language: English
• Published: Wiley 2019-09-01
• Series: Cancer Medicine
• Subjects: FAT4; gastric cancer; metastasis; miR‐107; proliferation
• Online Access: https://doi.org/10.1002/cam4.2396

Abstract Purpose To investigate the effect of miR‐107 on the growth and metastasis of gastric cancer (GC) and elucidate the probable mechanisms. Methods The expression of miR‐107 and FAT4 in GC tissues and cells were detected using qRT‐PCR. Bioinformatics and dual luciferase reporter gene assays were used to analyze the relationship between miR‐107 and FAT4. miR‐NC, miR‐107 inhibitor, pcDNA3.1‐FAT4 and siRNA‐FAT4 were transfected into AGS and MKN‐45 GC cell lines, respectively. The proliferation and migration abilities of GC cells after transfection were evaluated using the MTT assay, scratch test and transwell assay. The expression of epithelial‐mesenchymal transition (EMT) markers: E‐cadherin, N‐cadherin, vimentin and related proteins of the PI3K/AKT signaling pathway were determined using western blot. The xenograft tumors of nude mice were observed to assess the tumorigenicity of GC cells in vivo. Results MiR‐107 was up‐regulated, while FAT4 was down‐regulated in GC tissues and cells (P < 0.05); FAT4 was targeted and negatively regulated by miR‐107. Down‐regulating miR‐107 or up‐regulating FAT4 inhibited the GC cells proliferation, migration, invasion and tumorigenicity, and could also reduce the expression of N‐cadherin, vimentin, p‐PI3K and p‐Akt expression and up‐regulate E‐cadherin. Conclusions miR‐107 promotes growth and metastasis in GC via activation of PI3K‐AKT signaling by targeting FAT4, which may be a target for GC treatment.