MiR-155 promotes epithelial-mesenchymal transition in hepatocellular carcinoma cells through the activation of PI3K/SGK3/β-catenin signaling pathways.
Oncogenic mutations in PIK3CA, the gene encoding the catalytic subunit of phosphoinositide 3-kinase (PI3K), occur with high frequency in hepatocellular carcinoma (HCC). The protein kinase Akt is considered to be the primary effector of PI3K, but there is evidence to suggest that serum and glucocorticoid kinase 3 (SGK3) acts in an Akt-independent manner downstream of PI3K. In this report, we found that SGK3 promotes epithelial-mesenchymal transition (EMT) and reduces phosphorylation-dependent degradation of β-catenin in HCC cells. We determined that miR-155, previously shown to promote EMT, stimulates the expression of SGK3 by targeting and repressing P85α, thereby removing its inhibitory effect on PI3K-AKT signaling. These findings suggest that miR-155 promotes EMT and metastatic properties in HCC cells through activation of PI3K/SGK3/β-catenin signaling pathways.
Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Xin
X
Kong
Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Fengchao
F
Liu
Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Jian
J
Gao
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051176:beta Catenin; C495270:CTNNB1 protein, human; C524942:MIRN155 microRNA, human; C403243:SGK3 protein, human; D000099184:Serum-Glucocorticoid Regulated Kinases
SGK3; epithelial-mesenchymal transition; hepatocellular carcinoma; miR-155; phosphatidylinositol-3-kinase