title: MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN.
abstract: HER2-overexpressing breast cancers are characterized by frequent distant metastasis and often develop resistance after short-term effective treatment with the monoclonal antibody drug, trastuzumab. Here, we found that the oncogenic miRNA, miR-221, inhibited apoptosis, induced trastuzumab resistance and promoted metastasis of HER2-positive breast cancers. The tumor suppressor PTEN was identified as a miR-221 target; overexpression of PTEN abrogated the aforementioned miR-221-induced malignant phenotypes of the cells. These findings indicate that miR-221 may promote trastuzumab resistance and metastasis of HER2-positive breast cancers by targeting PTEN, suggesting its role as a potential biomarker for progression and poor prognosis, and as a novel target for trastuzumab-combined treatment of breast cancers.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University, Xi'an 710032; Fujian Provincial Cancer Hospital, the Teaching Hospital of Fujian Medical University, Fuzhou 350014, China.
authors.forename: Xingming
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wendong
authors.initials: W
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University, Xi'an 710032; Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Huayu
authors.initials: H
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Fujian Provincial Cancer Hospital, the Teaching Hospital of Fujian Medical University, Fuzhou 350014, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Angang
authors.initials: A
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lintao
authors.initials: L
authors.lastname: Jia
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C525709:MIR221, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human