Open AccessmiR‐107 regulates growth and metastasis of gastric cancer cells via activation of the PI3K‐AKT signaling pathway by down‐regulating FAT4
Author(s) -
Wang Li,
Li Kunkun,
Wang Chen,
Shi Xiaoxin,
Yang Huiyu
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2396
Subject(s) - vimentin , pi3k/akt/mtor pathway , epithelial–mesenchymal transition , cancer research , protein kinase b , transfection , cell growth , metastasis , signal transduction , biology , chemistry , microbiology and biotechnology , cell culture , cancer , immunology , immunohistochemistry , genetics
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.