title: MLH1 as a direct target of MiR-155 and a potential predictor of favorable prognosis in pancreatic cancer.
abstract: BACKGROUND
  The regulation of Mut L homologue 1 (MLH1) expression by microRNA (miR)-155 and its prognostic significance in pancreatic cancer (PC) remain to be elucidated. This study aimed to address the issues.
  
  
  METHODS
  MiR-155 mimics and inhibitor were transfected to PC cell lines, Panc-1 and Capan-1. Expression of MLH1 was subsequently evaluated. Then, luciferase activity was detected after miR-155 mimics and pRL-TK plasmids containing wild-type and mutant 3'UTRs of MLH1 mRNA were co-transfected. Finally, immunohistochemical staining for MLH1 was performed in PC samples.
  
  
  RESULTS
  Transfection of miR-155 mimics and inhibitor led to reversely altered protein expressions of miR-155 and MLH1, whereas the corresponding mRNA expressions were similar. A significant decrease in luciferase activity in the cells transfected with the wild-type pRL-TK plasmid was shown in contrast to those transfected with the mutant one. In addition, MLH1 was less expressed in tumor than in para-tumor tissues of PC. Extensive MLH1 expression was significantly associated with favorable differentiation and less lymph node metastasis. MLH1 expression was found to be a prognosticator in univariate analysis, and being of marginally significant impact in multivariate test.
  
  
  CONCLUSIONS
  MLH1 might serve as a direct target of miR-155 and a potential prognosis predictor in PC.
authors.affiliation: Department of General Surgery, National Laboratory of Medical Molecular Biology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Liu
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Zhao
authors.forename: Tai-Ping
authors.initials: TP
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Quan-Cai
authors.initials: QC
authors.lastname: Cui
authors.forename: Wei-Xun
authors.initials: WX
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: You
authors.forename: Ge
authors.initials: G
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Shu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C524942:MIRN155 microRNA, human; C501486:MLH1 protein, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000070957:MutL Protein Homolog 1