title: The expression of stem cell protein Piwil2 and piR-932 in breast cancer.
abstract: BACKGROUND
  To investigate the expression status of PIWIL2 and piR-932 in breast cancer stem cells and the role they could play in tumor cell growth and metastasis through Latexin.
  
  
  METHODS
  CD44(+)/CD24(-) tumor cells (CSC) from clinical specimens were sorted using flow cytometry. PIWIL2 expression status was detected in CSC cells by microarray analysis and 1086 breast cancer specimens by Western blot and immunohistochemistry staining. piR-932 expression was also detected in CSC cells by piRNA microarray assay. The relationship between the PIWIL2 protein and clinico-pathological parameters and prognosis was subsequently determined.
  
  
  RESULTS
  CSC cells are more likely to generate new tumors in mice and cell microspheres that are deficient in NOD/SCID compared to the control group. PIWIL2 protein was expressed higher in CSC cells compared to the control cells. In total, 334 (30.76%) of the 1086 breast cases showed high PIWIL2 expression. PIWIL2 was observed to be related to age, tumor size, histological type, tumor stage, and lymph node metastasis (all P < 0.05). Furthermore, we have found that one of the Piwi-interacting RNAs (piRNAs) called piR-932 expressed significantly higher in the breast cancer cells that were induced to EMT, and it could form immune complexes through immunoprecipitation with PIWIL2; in PIWIL2+ breast cancer stem cells, Latexin expression significantly reduced because of its promoter region CpG island methylation.
  
  
  CONCLUSIONS
  These results suggest that the combination of piR-932 and PIWIL2 may be a positive regulator in the process of breast cancer stem cells through promoting the methylation of Latexin, and they both could be the potential targets for blocking the metastasis of breast cancer.
authors.affiliation: Department of Breast Surgery, Second Hospital of Dalian Medical University, Dalian 116023, China. Electronic address: haozhang840514@gmail.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ren
authors.forename: Huanming
authors.initials: H
authors.lastname: Xu
authors.forename: Deyan
authors.initials: D
authors.lastname: Pang
authors.forename: Chao
authors.initials: C
authors.lastname: Duan
authors.forename: Caigang
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism*; D060565:Argonaute Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008207:Lymphatic Metastasis; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000941:Antigens; D060565:Argonaute Proteins; D014408:Biomarkers, Tumor; C086812:Lxn protein, rat; C486868:PIWIL2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: Breast cancer; Cancer stem cell; PIWIL2; piRNA