title: PGC-1 alpha interacts with microRNA-217 to functionally regulate breast cancer cell proliferation.
abstract: BACKGROUND
  In this study, we explored the functional mechanism of PPARg co-activator 1-alpha (PGC-1α) in regulating miR-217-mediated breast cancer development in vitro.
  
  
  METHODS
  Dual-luciferase activity assay was applied to examine the binding of miR-217 on PGC-1α gene. Breast cancer cell lines, MCF-7 and MDA-MB-231 were infected by lentivirus to constitutively downregulate miR-217. Its regulation on PGC-1α expression was investigated by qRT-PCR and western blot. PGC-1α gene was subsequently downregulated by siRNA in miR-217-downregulated breast cancer cells to examine its effect on cancer proliferation and cell-cycle progression. In addition, another downstream target gene of miR-217, DACH1, was further downregulated in breast cancer cells to investigate the functional association of PGC-1α and DACH1 in miR-217-mediated breast cancer regulation.
  
  
  RESULTS
  PGC-1α gene was directly bound by human miR-217. Downregulation of miR-217 in MCF-7 and MDA-MB-231 cells increased PGC-1α production at both mRNA and protein levels. SiRNA-mediated PGC-1α downregulation reversed the inhibition of miR-217-downregulaiton on breast cancer proliferation and cell-cycle progression. Moreover, siRNA-mediated DACH1 downregulation further reversed miR-217-downregulaiton induced inhibition on cancer proliferation and cell-cycle progression in PGC-1α downregulated MCF-7 and MDA-MB-231 cells.
  
  
  CONCLUSIONS
  MiR-217 is the upstream regulator of PGC-1α in breast cancer regulation in vitro, possibly independent of DACH1 signaling pathway.
authors.affiliation: Department of Pharmacology, Wuhan No. 1 Hospital, Tongji Medical College, Wuhan, Hebei Province, 430030, China.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Wuhan No. 1 Hospital, Tongji Medical College, Wuhan, Hebei Province, 430030, China.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Wuhan No. 1 Hospital, Tongji Medical College, Wuhan, Hebei Province, 430030, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Wuhan No. 1 Hospital, Tongji Medical College, Wuhan, Hebei Province, 430030, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, Wuhan No. 1 Hospital, Tongji Medical College, Wuhan, Hebei Province, 430030, China.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Wuhan No. 1 Hospital, Tongji Medical College, Wuhan, Hebei Province, 430030, China. Electronic address: geng_zhang@aol.com.
authors.forename: Geng
authors.initials: G
authors.lastname: Zhang
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C486747:DACH1 protein, human; D005136:Eye Proteins; C553315:MIRN217 microRNA, human; D035683:MicroRNAs; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D014157:Transcription Factors
keywords: Breast cancer; DACH1; Lentivirus; PGC-1 alpha; miR-217; siRNA