Silencing of DYRK2 increases cell proliferation but reverses CAM-DR in Non-Hodgkin's Lymphoma

DYRK2, a dual-specificity tyrosine-(Y)-phosphorylation regulated kinase gene, is involved in regulating many processes such as cell proliferation, cell differentiation and cytokinesis. DYRK2 also plays an important role in many cancers, such as breast cancer, non-small cell lung cancer and esophagea...

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Veröffentlicht in:International journal of biological macromolecules 2015-11, Vol.81, p.809-817
Hauptverfasser: Wang, Yuchan, Wu, Yaxun, Miao, Xiaobing, Zhu, Xinghua, Miao, Xianjing, He, Yunhua, Zhong, Fei, Ding, Linlin, Liu, Jing, Tang, Jie, Huang, Yuejiao, Xu, Xiaohong, He, Song
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container_title International journal of biological macromolecules
container_volume 81
creator Wang, Yuchan
Wu, Yaxun
Miao, Xiaobing
Zhu, Xinghua
Miao, Xianjing
He, Yunhua
Zhong, Fei
Ding, Linlin
Liu, Jing
Tang, Jie
Huang, Yuejiao
Xu, Xiaohong
He, Song
description DYRK2, a dual-specificity tyrosine-(Y)-phosphorylation regulated kinase gene, is involved in regulating many processes such as cell proliferation, cell differentiation and cytokinesis. DYRK2 also plays an important role in many cancers, such as breast cancer, non-small cell lung cancer and esophageal adenocarcinomas. In this study, we found that DYRK2 is associated with the proliferation of Non-Hodgkin's lymphoma (NHL) and cell adhesion mediated drug resistance (CAM-DR). Clinically, the mRNA and protein expression levels of DYRK2 are decreased in NHL tissues compared with reactive lymphoid hyperplasia tissues. Immunohistochemical analysis revealed that low expression of DYRK2 is associated with poor prognosis of NHL patients. Interestingly, knockdown of DYRK2 can promote cell proliferation via modulating cell cycle progression. Finally, we demonstrated that DYRK2 plays an important role in CAM-DR by regulating p27Kip1 expression. Importantly, DYRK2 knockdown reverses CAM-DR in NHL. Our research suggested that DYRK2 may be a novel therapeutic target for NHL.
doi_str_mv 10.1016/j.ijbiomac.2015.08.067
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DYRK2 also plays an important role in many cancers, such as breast cancer, non-small cell lung cancer and esophageal adenocarcinomas. In this study, we found that DYRK2 is associated with the proliferation of Non-Hodgkin's lymphoma (NHL) and cell adhesion mediated drug resistance (CAM-DR). Clinically, the mRNA and protein expression levels of DYRK2 are decreased in NHL tissues compared with reactive lymphoid hyperplasia tissues. Immunohistochemical analysis revealed that low expression of DYRK2 is associated with poor prognosis of NHL patients. Interestingly, knockdown of DYRK2 can promote cell proliferation via modulating cell cycle progression. Finally, we demonstrated that DYRK2 plays an important role in CAM-DR by regulating p27Kip1 expression. Importantly, DYRK2 knockdown reverses CAM-DR in NHL. 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Our research suggested that DYRK2 may be a novel therapeutic target for NHL.</description><subject>Adult</subject><subject>Aged</subject><subject>Cell Adhesion</subject><subject>Cell adhesion mediated drug resistance (CAM-DR)</subject><subject>Cell Cycle - genetics</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cyclin-Dependent Kinase Inhibitor p27</subject><subject>Disease Progression</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Dyrk Kinases</subject><subject>DYRK2</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Knockdown Techniques</subject><subject>Gene Silencing</subject><subject>Humans</subject><subject>Lymphoma, Large B-Cell, Diffuse - genetics</subject><subject>Lymphoma, Large B-Cell, Diffuse - metabolism</subject><subject>Lymphoma, Large B-Cell, Diffuse - pathology</subject><subject>Lymphoma, Non-Hodgkin - diagnosis</subject><subject>Lymphoma, Non-Hodgkin - genetics</subject><subject>Lymphoma, Non-Hodgkin - metabolism</subject><subject>Lymphoma, Non-Hodgkin - mortality</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Non-Hodgkin's lymphoma (NHL)</subject><subject>p27Kip1</subject><subject>Phenotype</subject><subject>Phosphorylation</subject><subject>Prognosis</subject><subject>Proliferation</subject><subject>Protein Serine-Threonine Kinases - genetics</subject><subject>Protein Serine-Threonine Kinases - metabolism</subject><subject>Protein-Tyrosine Kinases - genetics</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><issn>0141-8130</issn><issn>1879-0003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFv1DAQhS1URLeFv1D5BpcET-w4zo1qW1jEAtICBw7Isp1J8ZLEWztbqf--Xm3LtaeRZt6befMRcgGsBAby_bb0W-vDaFxZMahLpkommxdkAappC8YYPyELBgIKBZydkrOUtrkra1CvyGkluQAFzYL8-eEHnJyfbmjo6dXvzZeK-slFNAkTdTgMdBfD4HuMZvZhonY_04h3GA_z5eXX4mqTDfRbmIpV6G7--eltouv7cfc3h3tNXvZmSPjmsZ6TXx-vfy5Xxfr7p8_Ly3XhuFRzYS2zsrGmagS3opG2Nn3nKsF7xRy0ooO6VW1dc656EFXDneC8ryVX4KxBxc_Ju-PenPV2j2nWo0-H8GbCsE8amhpEC7IVWSqPUhdDShF7vYt-NPFeA9MHtHqrn9DqA1rNlM5os_Hi8cbejtj9tz2xzIIPRwHmT-88Rp2cz2yx8xHdrLvgn7vxAHUWjEY</recordid><startdate>20151101</startdate><enddate>20151101</enddate><creator>Wang, Yuchan</creator><creator>Wu, Yaxun</creator><creator>Miao, Xiaobing</creator><creator>Zhu, Xinghua</creator><creator>Miao, Xianjing</creator><creator>He, Yunhua</creator><creator>Zhong, Fei</creator><creator>Ding, Linlin</creator><creator>Liu, Jing</creator><creator>Tang, Jie</creator><creator>Huang, Yuejiao</creator><creator>Xu, Xiaohong</creator><creator>He, Song</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20151101</creationdate><title>Silencing of DYRK2 increases cell proliferation but reverses CAM-DR in Non-Hodgkin's Lymphoma</title><author>Wang, Yuchan ; Wu, Yaxun ; Miao, Xiaobing ; Zhu, Xinghua ; Miao, Xianjing ; He, Yunhua ; Zhong, Fei ; Ding, Linlin ; Liu, Jing ; Tang, Jie ; Huang, Yuejiao ; Xu, Xiaohong ; He, Song</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-bb0b67ba2743b476b5afdc243f80c194d1598955338f14273c433f56381cbae83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Cell Adhesion</topic><topic>Cell adhesion mediated drug resistance (CAM-DR)</topic><topic>Cell Cycle - genetics</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cyclin-Dependent Kinase Inhibitor p27</topic><topic>Disease Progression</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Dyrk Kinases</topic><topic>DYRK2</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Knockdown Techniques</topic><topic>Gene Silencing</topic><topic>Humans</topic><topic>Lymphoma, Large B-Cell, Diffuse - genetics</topic><topic>Lymphoma, Large B-Cell, Diffuse - metabolism</topic><topic>Lymphoma, Large B-Cell, Diffuse - pathology</topic><topic>Lymphoma, Non-Hodgkin - diagnosis</topic><topic>Lymphoma, Non-Hodgkin - genetics</topic><topic>Lymphoma, Non-Hodgkin - metabolism</topic><topic>Lymphoma, Non-Hodgkin - mortality</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Non-Hodgkin's lymphoma (NHL)</topic><topic>p27Kip1</topic><topic>Phenotype</topic><topic>Phosphorylation</topic><topic>Prognosis</topic><topic>Proliferation</topic><topic>Protein Serine-Threonine Kinases - genetics</topic><topic>Protein Serine-Threonine Kinases - metabolism</topic><topic>Protein-Tyrosine Kinases - genetics</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yuchan</creatorcontrib><creatorcontrib>Wu, Yaxun</creatorcontrib><creatorcontrib>Miao, Xiaobing</creatorcontrib><creatorcontrib>Zhu, Xinghua</creatorcontrib><creatorcontrib>Miao, Xianjing</creatorcontrib><creatorcontrib>He, Yunhua</creatorcontrib><creatorcontrib>Zhong, Fei</creatorcontrib><creatorcontrib>Ding, Linlin</creatorcontrib><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Tang, Jie</creatorcontrib><creatorcontrib>Huang, Yuejiao</creatorcontrib><creatorcontrib>Xu, Xiaohong</creatorcontrib><creatorcontrib>He, Song</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of biological macromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yuchan</au><au>Wu, Yaxun</au><au>Miao, Xiaobing</au><au>Zhu, Xinghua</au><au>Miao, Xianjing</au><au>He, Yunhua</au><au>Zhong, Fei</au><au>Ding, Linlin</au><au>Liu, Jing</au><au>Tang, Jie</au><au>Huang, Yuejiao</au><au>Xu, Xiaohong</au><au>He, Song</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Silencing of DYRK2 increases cell proliferation but reverses CAM-DR in Non-Hodgkin's Lymphoma</atitle><jtitle>International journal of biological macromolecules</jtitle><addtitle>Int J Biol Macromol</addtitle><date>2015-11-01</date><risdate>2015</risdate><volume>81</volume><spage>809</spage><epage>817</epage><pages>809-817</pages><issn>0141-8130</issn><eissn>1879-0003</eissn><abstract>DYRK2, a dual-specificity tyrosine-(Y)-phosphorylation regulated kinase gene, is involved in regulating many processes such as cell proliferation, cell differentiation and cytokinesis. DYRK2 also plays an important role in many cancers, such as breast cancer, non-small cell lung cancer and esophageal adenocarcinomas. In this study, we found that DYRK2 is associated with the proliferation of Non-Hodgkin's lymphoma (NHL) and cell adhesion mediated drug resistance (CAM-DR). Clinically, the mRNA and protein expression levels of DYRK2 are decreased in NHL tissues compared with reactive lymphoid hyperplasia tissues. Immunohistochemical analysis revealed that low expression of DYRK2 is associated with poor prognosis of NHL patients. Interestingly, knockdown of DYRK2 can promote cell proliferation via modulating cell cycle progression. Finally, we demonstrated that DYRK2 plays an important role in CAM-DR by regulating p27Kip1 expression. Importantly, DYRK2 knockdown reverses CAM-DR in NHL. 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subjects Adult
Aged
Cell Adhesion
Cell adhesion mediated drug resistance (CAM-DR)
Cell Cycle - genetics
Cell Line, Tumor
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p27
Disease Progression
Drug Resistance, Neoplasm - genetics
Dyrk Kinases
DYRK2
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Gene Silencing
Humans
Lymphoma, Large B-Cell, Diffuse - genetics
Lymphoma, Large B-Cell, Diffuse - metabolism
Lymphoma, Large B-Cell, Diffuse - pathology
Lymphoma, Non-Hodgkin - diagnosis
Lymphoma, Non-Hodgkin - genetics
Lymphoma, Non-Hodgkin - metabolism
Lymphoma, Non-Hodgkin - mortality
Male
Middle Aged
Non-Hodgkin's lymphoma (NHL)
p27Kip1
Phenotype
Phosphorylation
Prognosis
Proliferation
Protein Serine-Threonine Kinases - genetics
Protein Serine-Threonine Kinases - metabolism
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
RNA, Small Interfering - genetics
title Silencing of DYRK2 increases cell proliferation but reverses CAM-DR in Non-Hodgkin's Lymphoma
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