title: miR-33a suppresses the nuclear translocation of β-catenin to enhance gemcitabine sensitivity in human pancreatic cancer cells.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, partly due to its high level of drug resistance. β-Catenin is critical for drug resistance in pancreatic cancer, which occurs through multiple mechanisms. Here, we observed that miR-33a targeted the 3'UTR of β-catenin, inducing apoptosis and inhibiting the growth of human pancreatic cancer cells. Moreover, gemcitabine (GEM) treatment enhanced β-catenin expression by reducing miR-33a expression in a dose-dependent manner. GEM-resistant MiaPaCa-2(res) cells with a low level of miR-33a expression and high level of β-catenin expression adopted spindle-shaped morphologies, similar to their morphologies during the epithelial-to-mesenchymal transition (EMT), and their normal morphologies were restored by miR-33a overexpression. Furthermore, miR-33a downregulated β-catenin nuclear translocation, decreasing the transcription of survivin, cyclin D1, and MDR-1, and the protein expression of slug, vimentin, and N-cadherin, thereby mediating sensitization to GEM. Thus, miR-33a might function as a tumor suppressor to downregulate β-catenin expression, affecting cell growth, apoptosis, the EMT, and GEM resistance.
authors.affiliation: Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China. liyingyi@fudan.edu.cn.
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Bao-Hua
authors.initials: BH
authors.lastname: Yu
authors.affiliation: Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, 110084, Liaoning, China. 13309887041@163.com.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics; D000093542:Gemcitabine
chemical_list: C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D051176:beta Catenin; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Chemoresistance; Pancreatic cancer; miR-33a; β-Catenin