Abstract
BackgroundCyclophilin 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).MethodsThe 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.ResultsSuppression 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.ConclusionsThe suppression of CypA expression was correlated with decreased NSCLC cell tumorigenesis and metastasis.
Highlights
Cyclophilin A (CypA) is a cytosolic protein possessing peptidyl-prolyl isomerase activity that was recently reported to be overexpressed in several cancers
We detected the secreted matrix metalloproteinase 2 (MMP2) and matrix metallopeptidase 9 (MMP9), which are correlated with metastasis in non-small cell lung cancer (NSCLC), and we found that CypA enhanced the activity of secreted MMP9
We showed that the knockdown of CypA in human NSCLC cells inhibited cell proliferation, increased sensitivity to density-dependent inhibition, and down-regulated anchorage-independent cell growth
Summary
Cyclophilin A (CypA) is a cytosolic protein possessing peptidyl-prolyl isomerase activity that was recently reported to be overexpressed in several cancers. We explored the biology and molecular mechanism of CypA in non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of lung cancers. Treatment at an early stage, especially during the precancerous stage, Cyclophilins were originally identified as cell-binding proteins of the immunosuppressive drug, Cyclosporin A. The founding member of cyclophilins is cyclophilin A (CypA), an 18-kDa cytosolic protein that is ubiquitously expressed in prokaryotes and eukaryotes [3,4]. CypA plays important roles in protein folding, assembly, and trafficking, as well as immunoregulation and cell signaling [5,6,7,8]. CypA is implicated in several diseases, including viral infection, cardiovascular disease, inflammatory diseases, and cancer [9,10,11,12]
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