title: MiRNA-21 induces epithelial to mesenchymal transition and gemcitabine resistance via the PTEN/AKT pathway in breast cancer.
abstract: Acquisition of gemcitabine resistance in breast cancer has not been fully clarified. Prior studies suggest that miRNAs are important to chemoresistance in solid tumors and we confirmed that miR-21 is involved in the development of gemcitabine resistance. Epithelial-to-mesenchymal transition (EMT) and AKT pathway activation were noted to be important to this resistance as well. PTEN, a direct target gene of miR-21, was significantly downregulated in gemcitabine-resistant breast cancer cells and restoration of PTEN expression blocked miR-21-induced EMT and gemcitabine resistance. Our data offer novel insight into gemcitabine resistance in breast cancer and suggest that miR-21 may be used to predict optimal breast cancer therapy and may be a potential therapeutic target for reversing gemcitabine resistance.
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Rd, Shanghai, 200032, China.
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Rd, Shanghai, 200032, China.
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Tao
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Rd, Shanghai, 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Rd, Shanghai, 200032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Rd, Shanghai, 200032, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ni
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Rd, Shanghai, 200032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Rd, Shanghai, 200032, China.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong-An Rd, Shanghai, 200032, China. huxichun@aliyun.com.
authors.forename: Xi-Chun
authors.initials: XC
authors.lastname: Hu
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D003841:Deoxycytidine; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000093542:Gemcitabine
keywords: Breast cancer; Epithelial to mesenchymal transition (EMT); Gemcitabine resistance; miR-21