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Πέμπτη 5 Ιουλίου 2018

MiR-199a mediated the dissemination of human mantle cell lymphoma by interacting with the CCR7/CCL21 pair

Mantle cell lymphoma (MCL) is a rare but deadly subtype of non-Hodgkin's lymphomas because of it can progress rapidly and has a poor prognosis. MicroRNA-199a (miR-199a) is a potential diagnostic marker and therapeutic target for MCL patients. However, the function and molecular mechanisms of miRNA-199a in MCL cells are still unclear. In this study, we first analyzed the levels of miR-199a and C-C chemokine receptor 7 (CCR7) in the tumor tissues and tumor-adjacent tissues, and found that the level of miRNA-199a was lower, whereas the level of CCR7 was higher in tumor tissues. Moreover, overexpression of miR-199a in MCL cells downregulated the level of CCR7. Then, it was found that chemokine (C-C motif) ligand 21 (CCL21), a ligand of CCR7, promoted Granta-519 and Mino cell growth and migration in a concentration-dependent and time-dependent manner. Otherwise, the CCL21/CCR7 pair elevated the level of phosphorylation of protein kinase B and extracellular regulated protein kinases 1/2, upregulated the level of matrix metalloproteinases-2, matrix metalloproteinases-9, and the markers of the mesenchymal phenotype (N-cadherin and vimentin), as well as decreased the level of E-cadherin. However, the functions of CCL21/CCR7 in the growth, migration, and dissemination of MCL cells were decreased by overexpression of miR-199a. Thus, miR-199a inhibited the dissemination of MCL cells by reversing the function of CCL21/CCR7, providing a theoretical basis for miRNA-199a as a potential novel diagnostic marker and therapeutic target for MCL patients. Correspondence to Mingzhi Zhang, MD, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Science Avenue 100, Zhengzhou 450001, Henan Province, People's Republic of China Tel: +86 037 166 913 114; fax: +86 138 3856 5629; e-mail: zhangmingzhi891@163.com Received September 15, 2017 Accepted May 11, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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