title: MicroRNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4.
abstract: Pancreatic cancer patients are often resistant to chemotherapy treatment, which results in poor prognosis. The objective of this study was to delineate the mechanism by which miR-21 induces drug resistance to 5-fluorouracil (5-FU) in human pancreatic cancer cells (PATU8988 and PANC-1). We report that PATU8988 cells resistant to 5-FU express high levels of miR-21 in comparison to sensitive primary PATU8988 cells. Suppression of miR-21 expression in 5-Fu-resistant PATU8988 cells can alleviate its 5-FU resistance. Meanwhile, lentiviral vector-mediated overexpression of miR-21 not only conferred resistance to 5-FU but also promoted proliferation, migration, and invasion of PATU8988 and PANC-1 cells. The proresistance effects of miR-21 were attributed to the attenuated expression of tumor suppressor genes, including PTEN and PDCD4. Overexpression of PTEN and PDCD4 antagonized miR-21-induced resistance to 5-FU and migration activity. Our work demonstrates that miR-21 can confer drug resistance to 5-FU in pancreatic cancer cells by regulating the expression of tumor suppressor genes, as the target genes of miR-21, PTEN and PDCD4 can rescue 5-FU sensitivity and the phenotypic characteristics disrupted by miR-21.
authors: Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, China.|Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
authors: Xueju
authors: X
authors: Wei
authors: Department of General Surgery, Peking Union Medical College Hospital, CAMS & PUMC, Beijing, 100005, China.
authors: Weibin
authors: W
authors: Wang
authors: Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, China.|Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
authors: Lanlan
authors: L
authors: Wang
authors: Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, China.|Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
authors: Yuanyuan
authors: Y
authors: Zhang
authors: Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, China.|The First Hospital Affiliated To Henan University, Henan, 475000, China.
authors: Xian
authors: X
authors: Zhang
authors: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
authors: Mingtai
authors: M
authors: Chen
authors: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
authors: Fang
authors: F
authors: Wang
authors: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
authors: Jia
authors: J
authors: Yu
authors: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
authors: Yanni
authors: Y
authors: Ma
authors: Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, China.
authors: Guotao
authors: G
authors: Sun
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D005472:Fluorouracil
keywords: 5-Fluorouracil; PDCD4; PTEN; miR-21; pancreatic cancer