title: Downregulation of cyclophilin A by siRNA diminishes non-small cell lung cancer cell growth and metastasis via the regulation of matrix metallopeptidase 9.
abstract: BACKGROUND
  Cyclophilin A (CypA) is a cytosolic protein possessing peptidyl-prolyl isomerase activity that was recently reported to be overexpressed in several cancers. Here, we explored the biology and molecular mechanism of CypA in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  The expression of CypA in human NSCLC cell lines was detected by real-time reverse transcription PCR. The RNA interference-mediated knockdown of CypA was established in two NSCLC cell lines (95C and A549). 239836 CypA inhibitor was also used to suppress CypA activity. Tumorigenesis was assessed based on cellular proliferation, colony formation assays, and anchorage-independent growth assays; metastasis was assessed based on wound healing and transwell assays.
  
  
  RESULTS
  Suppression of CypA expression inhibited the cell growth and colony formation of A549 and 95C cells. CypA knockdown resulted in the inhibition of cell motility and invasion. Significantly, we show for the first time that CypA increased NSCLC cell invasion by regulating the activity of secreted matrix metallopeptidase 9 (MMP9). Likewise, suppression of CypA with 239836 CypA inhibitor decreased cell proliferation and MMP9 activity.
  
  
  CONCLUSIONS
  The suppression of CypA expression was correlated with decreased NSCLC cell tumorigenesis and metastasis.
authors.affiliation: Department of Cellular & Molecular Biology, Beijing TB and thoracic tumor research Institution/ Beijing Chest Hospital, Capital Medical University, 97 Beimachang, Tongzhou, Beijing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Qian
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Zhao
authors.forename: Mei
authors.initials: M
authors.lastname: Jiang
authors.forename: Wenyun
authors.initials: W
authors.lastname: Jia
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Baolan
authors.initials: B
authors.lastname: Li
authors.forename: Wentao
authors.initials: W
authors.lastname: Yue
mesh_terms: D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D021984:Cyclophilin A / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009362:Neoplasm Metastasis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004791:Enzyme Inhibitors; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D021984:Cyclophilin A