MicroRNA-375 targets PDK1 in pancreatic carcinoma and suppresses cell growth through the Akt signaling pathway.
MicroRNAs (miRNAs or miRs) are believed to have great potential for use as molecular targets in the diagnosis and treatment of cancer. In this study, we demonstrate that miR-375 is downregulated in pancreatic carcinoma (PC) tissues and PC cell lines. We found that miR-375 negatively regulates the expression of 3-phosphoinositide-dependent protein kinase 1 (PDK1) by directly targeting the 3'UTR of the PDK1 transcript. To investigate the biological roles and the potential mechanisms of action of miR‑375, we induced either the up- or downregulation of miR-375 expression by transfecting various PC cells with miR-375 mimics or an inhibitor. Our results revealed that the upregulation of miR-375 inhibited cell growth and induced cell apoptosis, while the downregulation of miR-375 with the inhibitor had the opposite effect. In addition, our data demonstrate that miR-375 suppresses the malignant behavior of PC cells through the Akt signaling pathway rather than mitogen-activated protein kinase (MAPK) signaling pathways. Taken together, our findings indicate that targeting miR-375 by a genetic approach may provide a novel strategy for the treatment of PC.
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Jian
J
Zhou
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Shiduo
S
Song
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Songbing
S
He
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Xinguo
X
Zhu
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Yi
Y
Zhang
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Bin
B
Yi
Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Bing
B
Zhang
Department of Gynaecology and Obstetrics, Suzhou Municipal Hospital, Suzhou, Jiangsu 215003, P.R. China.
Gongzhao
G
Qin
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Dechun
D
Li
D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases