title: MiR-125a regulates chemo-sensitivity to gemcitabine in human pancreatic cancer cells through targeting A20.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly human malignant diseases and the sixth leading cause of cancer-related deaths in China. Gemcitabine is the only first-line chemotherapeutic agent used for the palliative treatment of patients with PDAC, but chemo-resistance limits their efficacy. Here, we showed that miR-125a was up-regulated in chemo-resistant SW1990GZ cells when compared with SW1990 cells. Over-expression of miR-125a increased the chemo-resistance to gemcitabine in SW1990 cells, while down-regulation of miR-125a in SW1990GZ cells increased chemo-sensitivity to gemcitabine. By using bioinformatics analysis tool (Targetscan), the 3' untranslated region (3'UTR) of A20 gene was found to be a target of miR-125a. Luciferase reporter assay further confirmed that A20 3'UTR is a direct target of miR-125a. Over-expression of A20 in SW1990 cells increased chemo-sensitivity to gemcitabine, while knockdown of A20 in SW1990 cells promoted the chemo-resistance to gemcitabine. Finally, the expression level of miR-125a in pancreatic cancer tissues from chemo-sensitive patients was significantly lower than that from chemo-resistant patients, and was inversely correlated with the A20 mRNA levels. In conclusion, our results suggest that miR-125a promotes chemo-resistance to gemcitabine in pancreatic cells through targeting A20, which may provide novel therapeutic targets or molecular biomarkers for cancer therapy and improve tumor diagnosis or predictions of therapeutic responses.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, the Northern Jiangsu People's Hospital, Clinic Medical College of Yangzhou University, Yangzhou 225001, China docyao@126.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, the Northern Jiangsu People's Hospital, Clinic Medical College of Yangzhou University, Yangzhou 225001, China.
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, the Northern Jiangsu People's Hospital, Clinic Medical College of Yangzhou University, Yangzhou 225001, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, the Northern Jiangsu People's Hospital, Clinic Medical College of Yangzhou University, Yangzhou 225001, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, the Northern Jiangsu People's Hospital, Clinic Medical College of Yangzhou University, Yangzhou 225001, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, the Northern Jiangsu People's Hospital, Clinic Medical College of Yangzhou University, Yangzhou 225001, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Qian
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D000093542:Gemcitabine
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D003841:Deoxycytidine; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D000093542:Gemcitabine
keywords: A20; PDAC; chemo-resistance; gemcitabine; miR-125a