Abstract
Abstract Though ZNF 746 known as Parkin-interacting substrate (PARIS) was reported to repress PGC-1α and its target gene NRF-1 leading to the neurodegeneration in Parkinson's disease, its function in tumorigenesis has not been investigated until now. Thus, in the present study, the role of ZNF746 was investigated in the invasion and epithelial to mesenchymal transition (EMT) in ZNF746 overexpressed H460 non-small cell lung cancer (NSCLC) cells. Invasion assay showed that inhibition of ZNF 746 using siRNA transfection method inhibited the invasion of H460 cells using Boyden chamber. Real-time quantitative RT-PCR (RT-qPCR) revealed that the silencing of ZNF 746 attenuated the expression of matrix metalloproteinase (MMP) 1, MMP2 and MMP 9, but not MMP7 in H460 cells. Immunoblotting assay revealed that the expressions of E-cadherin of epithelial phenotype were up-regulated, while Slug was down-regulated in ZNF746 siRNA transfected H460 cells. Consistently, mRNA expression of E-cadherin was up-regulated while Vimentin or Slug, Twist, ZEB as EMT key transcriptional factors were suppressed in ZNF746 siRNA transfected H460 cells. Also, mRNA expression of transcriptional marker Nanog and Octamer-binding transcriptional factor 4 (OCT4) known to enhance malignancy and metastasis in lung adenocarcinoma was suppressed in ZNF746 siRNA transfected H460 cells. Interestingly, the endogenous expression of ZNF746 was induced in parallel with Twist at protein level during hypoxia. Moreover, we found that ZNF746 overexpressed cell lines, A549 and H460 were inhibited invasion and migration along with ZNF746 by melatonin. Overall, our findings suggest that ZNF746 can be an important target molecule in metastasis of lung cancer and melatonin may have the potential as an inhibitor of ZNF746 in NSCLC cells Citation Format: Bonglee Kim, Duckgue Lee, Sunghoon Kim. Melatonin suppresses invasion and epithelial to mesenchymal transition in non-small cell lung cancer cells via inhibition of ZNF746 signaling. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A30.
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