title: MiR-377 inhibits the proliferation of pancreatic cancer by targeting Pim-3.
abstract: MicroRNAs (miRNAs) play important roles in the regulation of various tumor biological processes including proliferation and apoptosis. MiR-377 has been implicated in many types of cancer, whereas its expressional feature and potential biological function in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we scanned the global miRNA expression profiles in PDAC from The Cancer Genome Atlas (TCGA) and found miR-377 was down-regulated significantly in PDAC. Then, its expression was measured in both pancreatic cancer tissues and cells; the data showed that miR-377 was de-regulated and inversely correlated with pathologic parameters of tumor growth or metastasis. We generated PDAC cell lines with stable overexpression or inhibition of miR-377, and our results indicated that miR-377 up-regulation significantly promoted cell viability, proliferation, and migration in PDAC cells, and also induced cell apoptosis and cell cycle arrest simultaneously. Binding-site predictions by bioinformatics showed that Pim-3 might be a potential target of miR-377. Luciferase reporter assay ulteriorly identified that miR-377 suppressed Pim-3 expression by binding the 3'-UTR. In tumor tissues, we also showed that the Pim-3 expression was inversely correlated with that of miR-377. Furthermore, stable ectopic miR-377 expression in pancreatic cancer cell lines suppressed Pim-3 expression, leading to the attenuation of Bad phosphorylation level at its Ser112and promoting cell apoptosis. Overall, these results reveal that miR-377 may have tumor growth suppression function by down-regulating Pim-3 kinase expression to inhibit both pancreatic tumor growth and migration, and induce cell apoptosis. Hence, miR-377 may be a potential diagnostic marker and therapeutic target.
authors.affiliation: Department of Hepatobiliary Surgery, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, No.10, Changjiangzhilu Road, Yu Zhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Hepatobiliary Surgery, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, No.10, Changjiangzhilu Road, Yu Zhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Menggang
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, No.10, Changjiangzhilu Road, Yu Zhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, No.10, Changjiangzhilu Road, Yu Zhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Hangwei
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Hepatobiliary Surgery, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, No.10, Changjiangzhilu Road, Yu Zhong District, Chongqing, 400042, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary Surgery, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, No.10, Changjiangzhilu Road, Yu Zhong District, Chongqing, 400042, People's Republic of China. yuantaotmmu@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Yuan
authors.affiliation: Department of Hepatobiliary Surgery, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, No.10, Changjiangzhilu Road, Yu Zhong District, Chongqing, 400042, People's Republic of China. chenpingsyd@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C494819:BAD protein, human; D014408:Biomarkers, Tumor; C534063:MIRN377 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D051025:bcl-Associated Death Protein; C499249:PIM3 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Apoptosis; Cell proliferation; Pancreatic ductal adenocarcinoma; Pim-3; miR-377