ING2-WTAP is a potential therapeutic target in non-small cell lung cancer
Non-small-cell lung carcinoma (NSCLC) is the most common kind of lung cancer, which is also the largest cause of cancer-linked deaths globally. A lack of effective prognostic biomarkers contributes to the poor prognosis of NSCLC. For better patient outcomes, NSCLC diagnosing, prognostic, and predict...
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Veröffentlicht in: | Biochemical and biophysical research communications 2022-05, Vol.605, p.31-38 |
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description | Non-small-cell lung carcinoma (NSCLC) is the most common kind of lung cancer, which is also the largest cause of cancer-linked deaths globally. A lack of effective prognostic biomarkers contributes to the poor prognosis of NSCLC. For better patient outcomes, NSCLC diagnosing, prognostic, and predictive biomarkers are critically needed. A component of the chromatin-modulatory complex that dampens gene expression, ING2 (inhibitor of growth family member 2), has been linked to cellular mechanisms that enhance tumor repression. Nevertheless, its role in human NSCLC is unclear. Herein, we observed that ING2 downregulation in NSCLC tissues correlates with poor NSCLC prognosis. Functional analysis illustrated that ING2 dampened growth, infiltration along with metastasis and blocked apoptosis of NSCLC cells in vitro, as well as in vivo. The mechanism might be implicated in the EMT (epithelial-mesenchymal transition) process. Mechanistically, we found that ING2 silencing suppresses the expressions of Wilms tumor 1-associated protein (WTAP) and that WTAP expression negatively correlates with ING2 expression. Moreover, rescue experiments illustrated that WTAP overexpression partially counteracts the effect of ING2 silencing on proliferation. Finally, we found that elevated WTAP levels correlate with poor NSCLC prognosis. These results highlight the prognostic and therapeutic potential of ING2-WTAP in NSCLC.
•NSCLC is among the leading causes of cancer-related deaths worldwide.•ING2 was associated with the poor prognosis of NSCLC patients.•ING2 inhibited cell apoptosis of NSCLC cells in vitro and in vivo.•ING2 silencing could decrease the expressions of the WTAP.•ING2-WTAP pathway plays an important role in the NSCLC. |
doi_str_mv | 10.1016/j.bbrc.2022.02.041 |
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•NSCLC is among the leading causes of cancer-related deaths worldwide.•ING2 was associated with the poor prognosis of NSCLC patients.•ING2 inhibited cell apoptosis of NSCLC cells in vitro and in vivo.•ING2 silencing could decrease the expressions of the WTAP.•ING2-WTAP pathway plays an important role in the NSCLC.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2022.02.041</identifier><identifier>PMID: 35306362</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Apoptosis ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - therapy ; Cell Cycle Proteins - metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Down-Regulation ; EMT ; Epithelial-Mesenchymal Transition - genetics ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; ING2 ; Lung Neoplasms - pathology ; NSCLC ; Progression ; Receptors, Cytoplasmic and Nuclear - metabolism ; RNA Splicing Factors - metabolism ; Tumor Suppressor Proteins ; WTAP</subject><ispartof>Biochemical and biophysical research communications, 2022-05, Vol.605, p.31-38</ispartof><rights>2022 Elsevier Inc.</rights><rights>Copyright © 2022 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-cdfaa875fd9a7ce3edda2636d799ad240dd4b28a29af9fd559677f55d1fb88843</citedby><cites>FETCH-LOGICAL-c356t-cdfaa875fd9a7ce3edda2636d799ad240dd4b28a29af9fd559677f55d1fb88843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2022.02.041$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35306362$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Hao</creatorcontrib><creatorcontrib>Wang, Shi-Jiang</creatorcontrib><creatorcontrib>Li, Zhi</creatorcontrib><creatorcontrib>Ma, Yan</creatorcontrib><creatorcontrib>Song, Yang-Rong</creatorcontrib><title>ING2-WTAP is a potential therapeutic target in non-small cell lung cancer</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Non-small-cell lung carcinoma (NSCLC) is the most common kind of lung cancer, which is also the largest cause of cancer-linked deaths globally. A lack of effective prognostic biomarkers contributes to the poor prognosis of NSCLC. For better patient outcomes, NSCLC diagnosing, prognostic, and predictive biomarkers are critically needed. A component of the chromatin-modulatory complex that dampens gene expression, ING2 (inhibitor of growth family member 2), has been linked to cellular mechanisms that enhance tumor repression. Nevertheless, its role in human NSCLC is unclear. Herein, we observed that ING2 downregulation in NSCLC tissues correlates with poor NSCLC prognosis. Functional analysis illustrated that ING2 dampened growth, infiltration along with metastasis and blocked apoptosis of NSCLC cells in vitro, as well as in vivo. The mechanism might be implicated in the EMT (epithelial-mesenchymal transition) process. Mechanistically, we found that ING2 silencing suppresses the expressions of Wilms tumor 1-associated protein (WTAP) and that WTAP expression negatively correlates with ING2 expression. Moreover, rescue experiments illustrated that WTAP overexpression partially counteracts the effect of ING2 silencing on proliferation. Finally, we found that elevated WTAP levels correlate with poor NSCLC prognosis. These results highlight the prognostic and therapeutic potential of ING2-WTAP in NSCLC.
•NSCLC is among the leading causes of cancer-related deaths worldwide.•ING2 was associated with the poor prognosis of NSCLC patients.•ING2 inhibited cell apoptosis of NSCLC cells in vitro and in vivo.•ING2 silencing could decrease the expressions of the WTAP.•ING2-WTAP pathway plays an important role in the NSCLC.</description><subject>Apoptosis</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - therapy</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Down-Regulation</subject><subject>EMT</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>ING2</subject><subject>Lung Neoplasms - pathology</subject><subject>NSCLC</subject><subject>Progression</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>RNA Splicing Factors - metabolism</subject><subject>Tumor Suppressor Proteins</subject><subject>WTAP</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFLwzAUxoMobk7_AQ-So5fOJG3SBryMoXMw1MNEbyFNXmdG184kFfzvbZl6FB7vXb7v43s_hC4pmVJCxc12WpbeTBlhbEr6yegRGlMiScIoyY7RmBAiEibp2widhbAlhNJMyFM0SnlKRCrYGC2XjwuWvK5nz9gFrPG-jdBEp2sc38HrPXTRGRy130DErsFN2yRhp-saG-hX3TUbbHRjwJ-jk0rXAS5-7gS93N-t5w_J6mmxnM9WiUm5iImxldZFzisrdW4gBWs167vYXEptWUaszUpWaCZ1JSvLuRR5XnFuaVUWRZGlE3R9yN379qODENXOhaGMbqDtgmIio5wyLgYpO0iNb0PwUKm9dzvtvxQlakCotmpAqAaEivST0d509ZPflTuwf5ZfZr3g9iCA_stPB14F46BHYJ0HE5Vt3X_532Q_gZI</recordid><startdate>20220521</startdate><enddate>20220521</enddate><creator>Cheng, Hao</creator><creator>Wang, Shi-Jiang</creator><creator>Li, Zhi</creator><creator>Ma, Yan</creator><creator>Song, Yang-Rong</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>20220521</creationdate><title>ING2-WTAP is a potential therapeutic target in non-small cell lung cancer</title><author>Cheng, Hao ; Wang, Shi-Jiang ; Li, Zhi ; Ma, Yan ; Song, Yang-Rong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-cdfaa875fd9a7ce3edda2636d799ad240dd4b28a29af9fd559677f55d1fb88843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Apoptosis</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - therapy</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Down-Regulation</topic><topic>EMT</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>ING2</topic><topic>Lung Neoplasms - pathology</topic><topic>NSCLC</topic><topic>Progression</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>RNA Splicing Factors - metabolism</topic><topic>Tumor Suppressor Proteins</topic><topic>WTAP</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Hao</creatorcontrib><creatorcontrib>Wang, Shi-Jiang</creatorcontrib><creatorcontrib>Li, Zhi</creatorcontrib><creatorcontrib>Ma, Yan</creatorcontrib><creatorcontrib>Song, Yang-Rong</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>Cheng, Hao</au><au>Wang, Shi-Jiang</au><au>Li, Zhi</au><au>Ma, Yan</au><au>Song, Yang-Rong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ING2-WTAP is a potential therapeutic target in non-small cell lung cancer</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2022-05-21</date><risdate>2022</risdate><volume>605</volume><spage>31</spage><epage>38</epage><pages>31-38</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Non-small-cell lung carcinoma (NSCLC) is the most common kind of lung cancer, which is also the largest cause of cancer-linked deaths globally. A lack of effective prognostic biomarkers contributes to the poor prognosis of NSCLC. For better patient outcomes, NSCLC diagnosing, prognostic, and predictive biomarkers are critically needed. A component of the chromatin-modulatory complex that dampens gene expression, ING2 (inhibitor of growth family member 2), has been linked to cellular mechanisms that enhance tumor repression. Nevertheless, its role in human NSCLC is unclear. Herein, we observed that ING2 downregulation in NSCLC tissues correlates with poor NSCLC prognosis. Functional analysis illustrated that ING2 dampened growth, infiltration along with metastasis and blocked apoptosis of NSCLC cells in vitro, as well as in vivo. The mechanism might be implicated in the EMT (epithelial-mesenchymal transition) process. Mechanistically, we found that ING2 silencing suppresses the expressions of Wilms tumor 1-associated protein (WTAP) and that WTAP expression negatively correlates with ING2 expression. Moreover, rescue experiments illustrated that WTAP overexpression partially counteracts the effect of ING2 silencing on proliferation. Finally, we found that elevated WTAP levels correlate with poor NSCLC prognosis. These results highlight the prognostic and therapeutic potential of ING2-WTAP in NSCLC.
•NSCLC is among the leading causes of cancer-related deaths worldwide.•ING2 was associated with the poor prognosis of NSCLC patients.•ING2 inhibited cell apoptosis of NSCLC cells in vitro and in vivo.•ING2 silencing could decrease the expressions of the WTAP.•ING2-WTAP pathway plays an important role in the NSCLC.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>35306362</pmid><doi>10.1016/j.bbrc.2022.02.041</doi><tpages>8</tpages></addata></record> |
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subjects | Apoptosis Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - therapy Cell Cycle Proteins - metabolism Cell Line, Tumor Cell Movement Cell Proliferation Down-Regulation EMT Epithelial-Mesenchymal Transition - genetics Gene Expression Regulation, Neoplastic Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans ING2 Lung Neoplasms - pathology NSCLC Progression Receptors, Cytoplasmic and Nuclear - metabolism RNA Splicing Factors - metabolism Tumor Suppressor Proteins WTAP |
title | ING2-WTAP is a potential therapeutic target in non-small cell lung cancer |
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