title: MiRNA-615-5p functions as a tumor suppressor in pancreatic ductal adenocarcinoma by targeting AKT2.
abstract: BACKGROUND
  Aberrant microRNA (miRNA) expression is associated with tumor development. This study aimed to elucidate the role of miR-615-5p in the development of pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  Locked nucleic acid in situ hybridization (LNA-ISH) was performed to compare miR-615-5p expression in patients between PDAC and matched adjacent normal tissues. Effects of miR-615-5p overexpression on cell proliferation, apoptosis, colony formation, migration, and invasion were determined in the pancreatic cancer cell lines PANC-1 and MIA PaCa-2. Effects of miR-615-5p on AKT2 were examined by dual-luciferase reporter assay. Lentivirus expressing miR-615 was used to create stable overexpression cell lines, which were subsequently used in mouse xenograft and metastasis models to assess tumor growth, apoptosis and metastasis.
  
  
  RESULTS
  miR-615-5p expression was significantly lower in PDAC than in adjacent normal tissues. Low levels of miR-615-5p were independently associated with poor prognosis (HR: 2.243, 95% CI: 1.190-4.227, P=0.013). AKT2 protein expression was inversely correlated with miR-615-5p expression (r=-0.3, P=0.003). miR-615-5p directly targeted the 3'-untranslated region of AKT2 mRNA and repressed its expression. miR-615-5p overexpression inhibited pancreatic cancer cell proliferation, migration, and invasion in vitro, and tumor growth and metastasis in vivo. Furthermore, miR-615-5p overexpression also induced pancreatic cancer cell apoptosis both in vitro and in vivo.
  
  
  CONCLUSIONS
  These results show that miR-615-5p inhibits pancreatic cancer cell proliferation, migration, and invasion by targeting AKT2. The data implicate miR-615-5p in the prognosis and treatment of PDAC.
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing, People's Republic of China.
authors: Yang
authors: Y
authors: Sun
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing, People's Republic of China.
authors: Tingting
authors: T
authors: Zhang
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing, People's Republic of China.
authors: Cuiping
authors: C
authors: Wang
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing, People's Republic of China.
authors: Xianglan
authors: X
authors: Jin
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing, People's Republic of China.
authors: Congwei
authors: C
authors: Jia
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing, People's Republic of China.
authors: Shuangni
authors: S
authors: Yu
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing, People's Republic of China.
authors: Jie
authors: J
authors: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*
chemical_list: C534344:MIRN615 microRNA, human; D035683:MicroRNAs; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt