title: miR-338-3p suppresses gastric cancer progression through a PTEN-AKT axis by targeting P-REX2a.
abstract: Results from recent studies suggest that aberrant microRNA expression is common in numerous cancers. Although miR-338-3p has been implicated in hepatocellular carcinoma, its role in gastric cancer is unknown. To this end, we report that miR-338-3p is downregulated in both gastric cancer tissue and cell lines. Forced expression of miR-338-3p inhibited cell proliferation and clonogenicity and induced a G1-S arrest as well as apoptosis in gastric cancer cells. Furthermore, P-Rex2a (PREX2) was identified as a direct target of miR-338-3p, and silencing P-Rex2a resulted in the same biologic effects of miR-338-3p expression in gastric cancer cells. Furthermore, both enforced expression of miR-338-3p or silencing of P-Rex2a resulted in activation of PTEN, leading to a decline in AKT phosphorylation. Also, miR-338-3p markedly inhibited the in vivo tumorigenicity in a nude mouse xenograft model system. These results demonstrate that miR-338-3p affects gastric cancer progression through PTEN-AKT signaling by targeting P-Rex2a in gastric cancer cells, which posits miR-338-3p as a novel strategy for gastric cancer treatment.
  
  
  CONCLUSIONS
  miR-338-3p acts as a novel tumor suppressor that blocks the growth of gastric cancer cells through PTEN-PI3K signaling by targeting P-Rex2a.
authors.affiliation: Xi'an Jiaotong University College of Medicine, Yanta Western Road 76, Xi'an 710061, China. hchen@mail.xjtu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Guo
authors.forename: Liying
authors.initials: L
authors.lastname: Liu
authors.forename: Jiayi
authors.initials: J
authors.lastname: Yao
authors.forename: Ruili
authors.initials: R
authors.lastname: Ma
authors.forename: Dongmin
authors.initials: D
authors.lastname: Chang
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Li
authors.forename: Tusheng
authors.initials: T
authors.lastname: Song
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D018450:Disease Progression; D059585:G1 Phase Cell Cycle Checkpoints / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C532050:MIRN338 microRNA, human; D035683:MicroRNAs; C490712:PREX2 protein, human; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human