title: The Interplay Between miR-148a and DNMT1 Might be Exploited for Pancreatic Cancer Therapy.
abstract: We discovered the expression level of miR-148a significantly decreased in pancreatic cancer tissues whereas that of DNMT1 increased. In ASPC-1 cancer cells, the overexpression of miR-148a led to a decreased level of DNMT1 and reduced the proliferation and metastasis of ASPC-1 cells. Moreover, the increased expression of miR-148a arrested the UTR methylation of p27, giving rise to an increased level of p27. Interestingly, it was shown that the DNMT1 inhibition enhanced the expression of miR-148a. In vivo studies demonstrated that the tumorigenesis of ASPC-1 was significantly arrested by either the overexpression of miR-148a or the inhibition of DNMT1.
authors.affiliation: Department of General Surgery, Rui Jin Hospital, School of Medicine, Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.forename: Xiaxing
authors.initials: X
authors.lastname: Deng
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Jianbin
authors.initials: J
authors.lastname: Jin
authors.forename: Xiongxiong
authors.initials: X
authors.lastname: Lu
authors.forename: Chenghong
authors.initials: C
authors.lastname: Peng
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.forename: Baiyong
authors.initials: B
authors.lastname: Shen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000628:therapy*; D020506:Untranslated Regions
chemical_list: C436291:CDKN1B protein, human; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D020506:Untranslated Regions; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse
keywords: DNMT1; Pancreatic cancer; Senescence; miR-148a; p27