title: MicroRNA-127 is aberrantly downregulated and acted as a functional tumor suppressor in human pancreatic cancer.
abstract: Pancreatic carcinoma is one of the most malignant human cancers. In this study, we intended to explore the molecular functional of microRNA-127 (miR-127) in regulating pancreatic cancer development both in vitro and in vivo. Quantitative real-time PCR (qRT-PCR) was performed to evaluate endogenous miR-127 expression in in vitro pancreatic cancer cell lines and in vivo clinical samples of pancreatic carcinoma. Lentiviral technology was applied to overexpress miR-127 in capan-1 and PANC-1 cells. Pancreatic cancer proliferation, cell-cycle progression, and invasion were assessed in vitro, and capan-1-derived tumorigenicity was evaluated in vivo. Dual-luciferase reporter assay and qRT-PCR were performed to assess the downstream target gene of miR-127 in pancreatic cancer, human Bcl-2-associated athanogene 5 (BAG5). BAG5 was subsequently upregulated in miR-127-overexpressed capan-1 and PANC-1 cells to evaluate its effect on pancreatic cancer progression. MiR-127 was preferentially downregulated in both pancreatic carcinoma cell lines and human pancreatic tumors. In lentivirus-infected capan-1 and PANC-1 cells, miR-127 overexpression significantly inhibited cancer progression, cell-cycle transition and invasion in vitro, as well as tumorigenicity in vivo. Human BAG5 was confirmed to be the downstream target of miR-127 in pancreatic cancer. Forced overexpression of BAG5 in capan-1 and PANC-1 cells reversed the tumor-suppressing effect of miR-127 on cancer development. MiR-127 is downregulated and acting as a tumor suppressor in pancreatic carcinoma. The functional regulation of miR-127 in pancreatic carcinoma is very likely through the inverse correlation of its downstream target gene of BAG5.
authors: Department of General Surgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, China.
authors: Yuan
authors: Y
authors: Yu
authors: Department of Gastroenterology Surgery, Songjiang Hospital Affiliated to The First People's Hospital of Shanghai Jiaotong University, 648 Middle Zhongshan Rd, Shanghai, 201600, China.
authors: Lei
authors: L
authors: Liu
authors: Department of Gastroenterology Surgery, Songjiang Hospital Affiliated to The First People's Hospital of Shanghai Jiaotong University, 648 Middle Zhongshan Rd, Shanghai, 201600, China.
authors: Ruirui
authors: R
authors: Ma
authors: Department of Gastroenterology Surgery, Songjiang Hospital Affiliated to The First People's Hospital of Shanghai Jiaotong University, 648 Middle Zhongshan Rd, Shanghai, 201600, China.
authors: Haibing
authors: H
authors: Gong
authors: Department of Gastroenterology, Songjiang Hospital Affiliated to The First People's Hospital of Shanghai Jiaotong University, 648 Middle Zhongshan Rd, Shanghai, 201600, China. sjzxxp@yeah.net.
authors: Ping
authors: P
authors: Xu
authors: Department of Gastroenterology Surgery, Songjiang Hospital Affiliated to The First People's Hospital of Shanghai Jiaotong University, 648 Middle Zhongshan Rd, Shanghai, 201600, China. wcj77843@aol.com.
authors: Congjun
authors: C
authors: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C496515:BAG5 protein, human; D014408:Biomarkers, Tumor; C547276:MIRN127 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: BAG5; Cancer migration; Cancer proliferation; Pancreatic carcinoma; Tumorigenicity; miR-127