Back to Journals » Cancer Management and Research » Volume 11

JAM3 functions as a novel tumor suppressor and is inactivated by DNA methylation in colorectal cancer

Authors Zhou D, Tang W, Zhang Y, An HX

Received 6 October 2018

Accepted for publication 12 February 2019

Published 27 March 2019 Volume 2019:11 Pages 2457—2470

DOI https://doi.org/10.2147/CMAR.S189937

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Rituraj Purohit


Dan Zhou,1–3,* Weiwei Tang,4,* Yun Zhang,1–3 Han-Xiang An1

1Department of Medical Oncology, Xiang’an Hospital of Xiamen University, Xiamen, Fujian, China; 2Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, China; 3Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy of Sciences, Xiamen, Fujian, China; 4Department of Medical Oncology, Cancer Hospital, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian, China

*These authors contributed equally to this work

Purpose: JAM3, an adhesion and transmigration regulatory element, is abundantly expressed in intestinal epithelial cells. However, its expression and function in colorectal cancer (CRC) remain unknown. In this study, we explored its epigenetic mechanism and biological role in CRC.
Patients and methods: Bioinformatics analysis was used to analyze the expression and methylation level of JAM3 in CRC. Methylation and expression status of JAM3 were then validated by quantitative methylation-specific PCR (qMSP) and quantitative PCR in tissues, plasma samples, and cell lines. Flow cytometry, Western blot, transwell, siRNA, colony formation, and transfection were used to evaluate the biological function of JAM3.
Results: We initially found that JAM3 was frequently methylated and downregulated in CRC based on bioinformatics tools. qMSP validation showed that the methylation levels of JAM3 were increased in 75% (18/24) of CRC tissues, 61% (11/18) plasma samples, and all four CRC cell lines and were significantly associated with tumor stage in CRC tissues. Moreover, JAM3 was downregulated in primary CRC tissues, plasma samples, and CRC cell lines as compared with that in nonmalignant controls, although its expression could be recovered after demethylation treatment. Restoration of JAM3 repressed CRC cell viability, colony formation, and migration. In addition, siRNA-mediated depletion of JAM3 in NCM460 cells improved the clonogenicity and migration capability, whereas it suppressed cell apoptosis and cell-cycle arrest. These functional effects were accompanied with alterations of several epithelial cell markers, including E-cadherin, vimentin, phosphor-β-catenin (ser552), and TJP1, which were responsible for epithelial–mesenchymal transition.
Conclusion: The findings indicated that JAM3 may be a novel tumor suppressor gene with epigenetic reduction in CRC and can be used as a potential noninvasive biomarker for CRC diagnosis.

Keywords: epigenetics, EMT, migration, metastasis


Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]