title: Let-7a mimic attenuates CCL18 induced breast cancer cell metastasis through Lin 28 pathway.
abstract: BACKGROUND
  MicroRNAs are believed to influence breast cancer cell tumorgenicity by interacting with the production of tumor associated macrophages. At this stage, this hypothesis lacks sufficient empirical evidence. Our study is an investigation of the effects of let-7a on the function of human breast cancer cell lines that had undergone chemokine ligand 18 (CCL18) stimulation.
  
  
  METHODS
  Two breast cancer cell lines MDA-MB-231 and MCF-7 were transfected with let-7a mimics with or without CCL18 simulation. The expression level of let-7a was evaluated with qRT-PCR. Our study examined cell proliferation, migration and cell cycles following let-7a treatment. The predicted target of let-7a was identified and confirmed in vitro by a dual luciferase reporter system. The associations between let-7a, CCL18 and target gene expression were evaluated using RT-PCR and the Western blotting method.
  
  
  RESULTS
  The downregulated expression level of let-7a was observed in both breast cancer cell lines. When compared to the control and CCL18 stimulation groups, cell proliferation and migration in MDA-MB-231 and MCF-7 cells were significantly inhibited by let-7a. Furthermore, the cell cycle was dramatically blocked at the G2/M phase. The luciferase reporter identified Lin28 as the direct binding target of let-7a in both breast cancer cell lines.
  
  
  CONCLUSIONS
  Upregulation of let-7a carries the potential to reverse CCL18 induced cell proliferation and migration alteration in breast cancer cells by regulating Lin28 expression. Our results provided evidence which suggests the use of let-7a as a therapeutic agent in the treatment of breast cancer.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, 453100, Xinxiang, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Xinxiang Medical University, 453003, Xinxiang, PR China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, 453100, Xinxiang, PR China.
authors.forename: De-Zhong
authors.initials: DZ
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, 453100, Xinxiang, PR China.
authors.forename: Xiang-Jie
authors.initials: XJ
authors.lastname: Fang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, 453100, Xinxiang, PR China.
authors.forename: Pei-Sheng
authors.initials: PS
authors.lastname: Sun
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, 453100, Xinxiang, PR China. Electronic address: professorhcxue@outlook.com.
authors.forename: Hui-Chao
authors.initials: HC
authors.lastname: Xue
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019742:Chemokines, CC / Q000494:pharmacology*; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects*; D014410:Tumor Stem Cell Assay; D048490:raf Kinases / Q000378:metabolism
chemical_list: D019742:Chemokines, CC; C000715187:Lin28A protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human; D048490:raf Kinases
keywords: Breast cancer; Cell cycle; Cell migration; MicroRNAs; Tumor associated macrophages