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Open Access Highly Accessed Research article

Downregulation of Cyclophilin A by siRNA diminishes non-small cell lung cancer cell growth and metastasis via the regulation of matrix metallopeptidase 9

Zhe Qian1, Xiaoting Zhao1, Mei Jiang1, Wenyun Jia1, Chunyan Zhang1, Yue Wang1, Baolan Li2* and Wentao Yue1*

Author Affiliations

1 Department of Cellular & Molecular Biology, Beijing TB and thoracic tumor research Institution/ Beijing Chest Hospital, Capital Medical University, 97 Beimachang, Tongzhou, Beijing, China

2 General medicine Department, Beijing Chest Hospital, Capital Medical University, 97 Beimachang, Tongzhou, Beijing, China

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BMC Cancer 2012, 12:442  doi:10.1186/1471-2407-12-442

Published: 2 October 2012

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.

Keywords:
Cyclophilin A; Non-small cell lung cancer; Proliferation; Metastasis; Matrix metallopeptidase 9