UNC93B1 promotes tumoral growth by controlling the secretion level of granulocyte macrophage colony-stimulating factor in human oral cancer

Unc-93 homolog B1 (UNC93B1), a transmembrane protein, is correlated with immune diseases, such as influenza, herpes simplex encephalitis, and the pathogenesis of systemic lupus erythematosus; however, the role of UNC93B1 in cancers including human oral squamous cell carcinomas (OSCCs) remains unknow...

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Veröffentlicht in:Biochemical and biophysical research communications 2019-05, Vol.513 (1), p.81-87
Hauptverfasser: Wagai, Sho, Kasamatsu, Atsushi, Iyoda, Manabu, Hayashi, Fumihiko, Hiroshima, Kazuya, Yoshimura, Shusaku, Miyamoto, Isao, Nakashima, Dai, Endo-Sakamoto, Yosuke, Shiiba, Masashi, Tanzawa, Hideki, Uzawa, Katsuhiro
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container_title Biochemical and biophysical research communications
container_volume 513
creator Wagai, Sho
Kasamatsu, Atsushi
Iyoda, Manabu
Hayashi, Fumihiko
Hiroshima, Kazuya
Yoshimura, Shusaku
Miyamoto, Isao
Nakashima, Dai
Endo-Sakamoto, Yosuke
Shiiba, Masashi
Tanzawa, Hideki
Uzawa, Katsuhiro
description Unc-93 homolog B1 (UNC93B1), a transmembrane protein, is correlated with immune diseases, such as influenza, herpes simplex encephalitis, and the pathogenesis of systemic lupus erythematosus; however, the role of UNC93B1 in cancers including human oral squamous cell carcinomas (OSCCs) remains unknown. In the current study, we investigated the UNC93B1expression level in OSCCs using quantitative reverse transcription-polymerase chain reaction, immunoblot analysis, and immunohistochemistry. Our data showed that UNC93B1 mRNA and protein expressions increased markedly (p 
doi_str_mv 10.1016/j.bbrc.2019.03.172
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In the current study, we investigated the UNC93B1expression level in OSCCs using quantitative reverse transcription-polymerase chain reaction, immunoblot analysis, and immunohistochemistry. Our data showed that UNC93B1 mRNA and protein expressions increased markedly (p &lt; 0.05) in OSCCs compared with normal cells and tissues and that high expression of UNC93B1 in OSCCs was related closely to tumoral size. UNC93B1 knockdown (shUNC93B1) OSCC cells showed decreased cellular proliferation by cell-cycle arrest in the G1 phase with up-regulation of p21Cip1 and down-regulation of CDK4, CDK6, cyclin D1, and cyclin E. We also found that granulocyte macrophage colony-stimulating factor (GM-CSF) was down-regulated significantly (p &lt; 0.05) in shUNC93B1 OSCC cells. Moreover, inactivation of GM-CSF using neutralization antibody led to cell-cycle arrest at the G1 phase similar to the phenotype of the shUNC93B1 cells. The current findings indicated that UNC93B1 might play a crucial role in OSCC by controlling the secretion level of GM-CSF involved in tumoral growth and could be a potential therapeutic target for OSCCs. •Unc-93 homolog B1 (UNC93B1) plays a significant role in tumoral growth.•UNC93B1 regulates cell-cycle arrest at the G1 phase in oral squamous cell carcinoma.•Down-regulated UNC93B1 stops granulocyte macrophage colony-stimulating factor.•UNC93B1 may control tumors via granulocyte macrophage colony-stimulating factor.•UNC93B1 may be a therapeutic target for oral squamous cell carcinoma.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2019.03.172</identifier><identifier>PMID: 30935694</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Cell-cycle arrest at G1 phase ; Cells, Cultured ; Gene Expression Regulation, Neoplastic ; GM-CSF ; Granulocyte-Macrophage Colony-Stimulating Factor - genetics ; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism ; Humans ; Membrane Transport Proteins - genetics ; Membrane Transport Proteins - metabolism ; Mouth Neoplasms - genetics ; Mouth Neoplasms - metabolism ; Mouth Neoplasms - pathology ; OSCC ; Tumoral growth ; UNC93B1</subject><ispartof>Biochemical and biophysical research communications, 2019-05, Vol.513 (1), p.81-87</ispartof><rights>2019 Elsevier Inc.</rights><rights>Copyright © 2019 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-cc4832985dcfe84026c869eee61ea7151721f778b3e1b60fc517569a5209ad893</citedby><cites>FETCH-LOGICAL-c356t-cc4832985dcfe84026c869eee61ea7151721f778b3e1b60fc517569a5209ad893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X19305728$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30935694$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wagai, Sho</creatorcontrib><creatorcontrib>Kasamatsu, Atsushi</creatorcontrib><creatorcontrib>Iyoda, Manabu</creatorcontrib><creatorcontrib>Hayashi, Fumihiko</creatorcontrib><creatorcontrib>Hiroshima, Kazuya</creatorcontrib><creatorcontrib>Yoshimura, Shusaku</creatorcontrib><creatorcontrib>Miyamoto, Isao</creatorcontrib><creatorcontrib>Nakashima, Dai</creatorcontrib><creatorcontrib>Endo-Sakamoto, Yosuke</creatorcontrib><creatorcontrib>Shiiba, Masashi</creatorcontrib><creatorcontrib>Tanzawa, Hideki</creatorcontrib><creatorcontrib>Uzawa, Katsuhiro</creatorcontrib><title>UNC93B1 promotes tumoral growth by controlling the secretion level of granulocyte macrophage colony-stimulating factor in human oral cancer</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Unc-93 homolog B1 (UNC93B1), a transmembrane protein, is correlated with immune diseases, such as influenza, herpes simplex encephalitis, and the pathogenesis of systemic lupus erythematosus; however, the role of UNC93B1 in cancers including human oral squamous cell carcinomas (OSCCs) remains unknown. In the current study, we investigated the UNC93B1expression level in OSCCs using quantitative reverse transcription-polymerase chain reaction, immunoblot analysis, and immunohistochemistry. Our data showed that UNC93B1 mRNA and protein expressions increased markedly (p &lt; 0.05) in OSCCs compared with normal cells and tissues and that high expression of UNC93B1 in OSCCs was related closely to tumoral size. UNC93B1 knockdown (shUNC93B1) OSCC cells showed decreased cellular proliferation by cell-cycle arrest in the G1 phase with up-regulation of p21Cip1 and down-regulation of CDK4, CDK6, cyclin D1, and cyclin E. We also found that granulocyte macrophage colony-stimulating factor (GM-CSF) was down-regulated significantly (p &lt; 0.05) in shUNC93B1 OSCC cells. Moreover, inactivation of GM-CSF using neutralization antibody led to cell-cycle arrest at the G1 phase similar to the phenotype of the shUNC93B1 cells. The current findings indicated that UNC93B1 might play a crucial role in OSCC by controlling the secretion level of GM-CSF involved in tumoral growth and could be a potential therapeutic target for OSCCs. •Unc-93 homolog B1 (UNC93B1) plays a significant role in tumoral growth.•UNC93B1 regulates cell-cycle arrest at the G1 phase in oral squamous cell carcinoma.•Down-regulated UNC93B1 stops granulocyte macrophage colony-stimulating factor.•UNC93B1 may control tumors via granulocyte macrophage colony-stimulating factor.•UNC93B1 may be a therapeutic target for oral squamous cell carcinoma.</description><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Cycle Checkpoints</subject><subject>Cell Line, Tumor</subject><subject>Cell-cycle arrest at G1 phase</subject><subject>Cells, Cultured</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>GM-CSF</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - genetics</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</subject><subject>Humans</subject><subject>Membrane Transport Proteins - genetics</subject><subject>Membrane Transport Proteins - metabolism</subject><subject>Mouth Neoplasms - genetics</subject><subject>Mouth Neoplasms - metabolism</subject><subject>Mouth Neoplasms - pathology</subject><subject>OSCC</subject><subject>Tumoral growth</subject><subject>UNC93B1</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v1DAUtBCILoU_wAH5yCXh2U6yscQFVnxJVbm0Um-W47zseuXYi-202t_An8bLFo6VnmTpaWaeZ4aQtwxqBqz7sK-HIZqaA5M1iJqt-TOyYiCh4gya52QFAF3FJbu7IK9S2gMw1nTyJbkQIEXbyWZFft9eb6T4zOghhjlkTDQvc4ja0W0MD3lHhyM1wecYnLN-S_MOaUITMdvgqcN7dDRMBaz94oI5ZqSzNjEcdnqLhemCP1Yp23lxOp8EJm1yiNR6ultm7enfW0Z7g_E1eTFpl_DN43tJbr9-udl8r65-fvux-XRVmfLpXBnT9ILLvh3NhH0DvDN9JxGxY6jXrC05sGm97geBbOhgMmVTzOqWg9RjL8UleX_WLZ5_LZiymm0y6Jz2GJakOIcyomtFgfIztFhKKeKkDtHOOh4VA3UqQe3VqQR1KkGBUOV4Ib171F-GGcf_lH-pF8DHMwCLy3uLUSVjsUQw2ogmqzHYp_T_AArCmp0</recordid><startdate>20190521</startdate><enddate>20190521</enddate><creator>Wagai, Sho</creator><creator>Kasamatsu, Atsushi</creator><creator>Iyoda, Manabu</creator><creator>Hayashi, Fumihiko</creator><creator>Hiroshima, Kazuya</creator><creator>Yoshimura, Shusaku</creator><creator>Miyamoto, Isao</creator><creator>Nakashima, Dai</creator><creator>Endo-Sakamoto, Yosuke</creator><creator>Shiiba, Masashi</creator><creator>Tanzawa, Hideki</creator><creator>Uzawa, Katsuhiro</creator><general>Elsevier Inc</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>20190521</creationdate><title>UNC93B1 promotes tumoral growth by controlling the secretion level of granulocyte macrophage colony-stimulating factor in human oral cancer</title><author>Wagai, Sho ; Kasamatsu, Atsushi ; Iyoda, Manabu ; Hayashi, Fumihiko ; Hiroshima, Kazuya ; Yoshimura, Shusaku ; Miyamoto, Isao ; Nakashima, Dai ; Endo-Sakamoto, Yosuke ; Shiiba, Masashi ; Tanzawa, Hideki ; Uzawa, Katsuhiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-cc4832985dcfe84026c869eee61ea7151721f778b3e1b60fc517569a5209ad893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell Cycle Checkpoints</topic><topic>Cell Line, Tumor</topic><topic>Cell-cycle arrest at G1 phase</topic><topic>Cells, Cultured</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>GM-CSF</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - genetics</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</topic><topic>Humans</topic><topic>Membrane Transport Proteins - genetics</topic><topic>Membrane Transport Proteins - metabolism</topic><topic>Mouth Neoplasms - genetics</topic><topic>Mouth Neoplasms - metabolism</topic><topic>Mouth Neoplasms - pathology</topic><topic>OSCC</topic><topic>Tumoral growth</topic><topic>UNC93B1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wagai, Sho</creatorcontrib><creatorcontrib>Kasamatsu, Atsushi</creatorcontrib><creatorcontrib>Iyoda, Manabu</creatorcontrib><creatorcontrib>Hayashi, Fumihiko</creatorcontrib><creatorcontrib>Hiroshima, Kazuya</creatorcontrib><creatorcontrib>Yoshimura, Shusaku</creatorcontrib><creatorcontrib>Miyamoto, Isao</creatorcontrib><creatorcontrib>Nakashima, Dai</creatorcontrib><creatorcontrib>Endo-Sakamoto, Yosuke</creatorcontrib><creatorcontrib>Shiiba, Masashi</creatorcontrib><creatorcontrib>Tanzawa, Hideki</creatorcontrib><creatorcontrib>Uzawa, Katsuhiro</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>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wagai, Sho</au><au>Kasamatsu, Atsushi</au><au>Iyoda, Manabu</au><au>Hayashi, Fumihiko</au><au>Hiroshima, Kazuya</au><au>Yoshimura, Shusaku</au><au>Miyamoto, Isao</au><au>Nakashima, Dai</au><au>Endo-Sakamoto, Yosuke</au><au>Shiiba, Masashi</au><au>Tanzawa, Hideki</au><au>Uzawa, Katsuhiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>UNC93B1 promotes tumoral growth by controlling the secretion level of granulocyte macrophage colony-stimulating factor in human oral cancer</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2019-05-21</date><risdate>2019</risdate><volume>513</volume><issue>1</issue><spage>81</spage><epage>87</epage><pages>81-87</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Unc-93 homolog B1 (UNC93B1), a transmembrane protein, is correlated with immune diseases, such as influenza, herpes simplex encephalitis, and the pathogenesis of systemic lupus erythematosus; however, the role of UNC93B1 in cancers including human oral squamous cell carcinomas (OSCCs) remains unknown. In the current study, we investigated the UNC93B1expression level in OSCCs using quantitative reverse transcription-polymerase chain reaction, immunoblot analysis, and immunohistochemistry. Our data showed that UNC93B1 mRNA and protein expressions increased markedly (p &lt; 0.05) in OSCCs compared with normal cells and tissues and that high expression of UNC93B1 in OSCCs was related closely to tumoral size. UNC93B1 knockdown (shUNC93B1) OSCC cells showed decreased cellular proliferation by cell-cycle arrest in the G1 phase with up-regulation of p21Cip1 and down-regulation of CDK4, CDK6, cyclin D1, and cyclin E. We also found that granulocyte macrophage colony-stimulating factor (GM-CSF) was down-regulated significantly (p &lt; 0.05) in shUNC93B1 OSCC cells. Moreover, inactivation of GM-CSF using neutralization antibody led to cell-cycle arrest at the G1 phase similar to the phenotype of the shUNC93B1 cells. The current findings indicated that UNC93B1 might play a crucial role in OSCC by controlling the secretion level of GM-CSF involved in tumoral growth and could be a potential therapeutic target for OSCCs. •Unc-93 homolog B1 (UNC93B1) plays a significant role in tumoral growth.•UNC93B1 regulates cell-cycle arrest at the G1 phase in oral squamous cell carcinoma.•Down-regulated UNC93B1 stops granulocyte macrophage colony-stimulating factor.•UNC93B1 may control tumors via granulocyte macrophage colony-stimulating factor.•UNC93B1 may be a therapeutic target for oral squamous cell carcinoma.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30935694</pmid><doi>10.1016/j.bbrc.2019.03.172</doi><tpages>7</tpages></addata></record>
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subjects Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Cycle Checkpoints
Cell Line, Tumor
Cell-cycle arrest at G1 phase
Cells, Cultured
Gene Expression Regulation, Neoplastic
GM-CSF
Granulocyte-Macrophage Colony-Stimulating Factor - genetics
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Humans
Membrane Transport Proteins - genetics
Membrane Transport Proteins - metabolism
Mouth Neoplasms - genetics
Mouth Neoplasms - metabolism
Mouth Neoplasms - pathology
OSCC
Tumoral growth
UNC93B1
title UNC93B1 promotes tumoral growth by controlling the secretion level of granulocyte macrophage colony-stimulating factor in human oral cancer
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