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.
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: M V Perini; A L Montagnini; J Jukemura; S Penteado; E E Abdo; R Patzina; I Cecconello; J E M Cunha Journal: HPB (Oxford) Date: 2008 Impact factor: 3.647
Authors: H Nakamura; K Tanimoto; K Hiyama; M Yunokawa; T Kawamoto; Y Kato; K Yoshiga; L Poellinger; E Hiyama; M Nishiyama Journal: Oncogene Date: 2008-03-17 Impact factor: 9.867
Authors: Yaacov R Lawrence; Jennifer Moughan; Anthony M Magliocco; Alexander C Klimowicz; William F Regine; Rex B Mowat; Thomas A DiPetrillo; William Small; Jeffry P Simko; Talia Golan; Kathryn A Winter; Chandan Guha; Christopher H Crane; Adam P Dicker Journal: Cancer Date: 2017-10-20 Impact factor: 6.860