MIEN1 on the 17q12 amplicon facilitates the malignant behaviors of gastric cancer via activating IL-6/JAK2/STAT3 pathway
Oncogene amplification is a significant factor contributing to poor prognosis and limited treatment in patients with advanced gastric cancer. Therefore, identifying amplified oncogenes and elucidating their oncogenic mechanisms will provide reliable therapeutic targets for the clinical treatment of...
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| Veröffentlicht in: | The international journal of biochemistry & cell biology 2024-11, Vol.176, p.106666, Article 106666 |
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| container_title | The international journal of biochemistry & cell biology |
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| creator | Lin, Jing Wang, Dong Zhou, Jiahui Bai, Jing Sun, Shouzhen Jia, Xueyuan Liang, Xiao Fu, Songbin Yu, Jingcui |
| description | Oncogene amplification is a significant factor contributing to poor prognosis and limited treatment in patients with advanced gastric cancer. Therefore, identifying amplified oncogenes and elucidating their oncogenic mechanisms will provide reliable therapeutic targets for the clinical treatment of gastric cancer. In this study, we identify a high amplification of 17q12, which includes five oncogenes that are co-amplified and co-overexpressed with ERBB2 using array comparative genomic hybridization, with migration and invasion enhancer 1 (MIEN1) being particularly highlighted for its clinical significance, function, and role in gastric cancer progression. By detecting MIEN1 copy number and expression level across eight gastric cancer cell lines and in tissue microarrays from 543 primary gastric cancer tissues, we found that MIEN1 amplification and overexpression correlated with sex and Lauren’s intestinal type classification of gastric cancer. Besides that, elevated MIEN1 expression was associated with poorer patient survival. In vitro experiments have shown that MIEN1 overexpression enhanced cell proliferation, invasion, and migration, whereas MIEN1 knockdown reversed these malignant phenotypes in vitro. Furthermore, MIEN1 knockdown inhibited tumorigenesis and metastasis of gastric cancer cells in nude mice. Mechanistically, MIEN1 activates the IL-6/JAK2/STAT3 signaling pathway, which drives the proliferation, invasion, and migration of gastric cancer cells. This study demonstrates that MIEN1 contributes to the malignant behavior of gastric cancer through the IL-6/JAK2/STAT3 pathway, suggesting that MIEN1 could serve as a valuable therapeutic target for gastric cancer. |
| doi_str_mv | 10.1016/j.biocel.2024.106666 |
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Therefore, identifying amplified oncogenes and elucidating their oncogenic mechanisms will provide reliable therapeutic targets for the clinical treatment of gastric cancer. In this study, we identify a high amplification of 17q12, which includes five oncogenes that are co-amplified and co-overexpressed with ERBB2 using array comparative genomic hybridization, with migration and invasion enhancer 1 (MIEN1) being particularly highlighted for its clinical significance, function, and role in gastric cancer progression. By detecting MIEN1 copy number and expression level across eight gastric cancer cell lines and in tissue microarrays from 543 primary gastric cancer tissues, we found that MIEN1 amplification and overexpression correlated with sex and Lauren’s intestinal type classification of gastric cancer. Besides that, elevated MIEN1 expression was associated with poorer patient survival. In vitro experiments have shown that MIEN1 overexpression enhanced cell proliferation, invasion, and migration, whereas MIEN1 knockdown reversed these malignant phenotypes in vitro. Furthermore, MIEN1 knockdown inhibited tumorigenesis and metastasis of gastric cancer cells in nude mice. Mechanistically, MIEN1 activates the IL-6/JAK2/STAT3 signaling pathway, which drives the proliferation, invasion, and migration of gastric cancer cells. This study demonstrates that MIEN1 contributes to the malignant behavior of gastric cancer through the IL-6/JAK2/STAT3 pathway, suggesting that MIEN1 could serve as a valuable therapeutic target for gastric cancer.</description><identifier>ISSN: 1357-2725</identifier><identifier>ISSN: 1878-5875</identifier><identifier>EISSN: 1878-5875</identifier><identifier>DOI: 10.1016/j.biocel.2024.106666</identifier><identifier>PMID: 39343060</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Amplification ; Animals ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Chr17q12 ; Female ; Gastric cancer ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; IL-6/JAK2/STAT3 ; Interleukin-6 - genetics ; Interleukin-6 - metabolism ; Janus Kinase 2 - genetics ; Janus Kinase 2 - metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; MIEN1 ; Overexpression ; Signal Transduction ; STAT3 Transcription Factor - genetics ; STAT3 Transcription Factor - metabolism ; Stomach Neoplasms - genetics ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - pathology</subject><ispartof>The international journal of biochemistry & cell biology, 2024-11, Vol.176, p.106666, Article 106666</ispartof><rights>2024 Elsevier Ltd</rights><rights>Copyright © 2024 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c241t-3db7d8456adacd03a09d6d591d2e7343c2adf4f335937354802e28fb40a3c79e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biocel.2024.106666$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39343060$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Jing</creatorcontrib><creatorcontrib>Wang, Dong</creatorcontrib><creatorcontrib>Zhou, Jiahui</creatorcontrib><creatorcontrib>Bai, Jing</creatorcontrib><creatorcontrib>Sun, Shouzhen</creatorcontrib><creatorcontrib>Jia, Xueyuan</creatorcontrib><creatorcontrib>Liang, Xiao</creatorcontrib><creatorcontrib>Fu, Songbin</creatorcontrib><creatorcontrib>Yu, Jingcui</creatorcontrib><title>MIEN1 on the 17q12 amplicon facilitates the malignant behaviors of gastric cancer via activating IL-6/JAK2/STAT3 pathway</title><title>The international journal of biochemistry & cell biology</title><addtitle>Int J Biochem Cell Biol</addtitle><description>Oncogene amplification is a significant factor contributing to poor prognosis and limited treatment in patients with advanced gastric cancer. Therefore, identifying amplified oncogenes and elucidating their oncogenic mechanisms will provide reliable therapeutic targets for the clinical treatment of gastric cancer. In this study, we identify a high amplification of 17q12, which includes five oncogenes that are co-amplified and co-overexpressed with ERBB2 using array comparative genomic hybridization, with migration and invasion enhancer 1 (MIEN1) being particularly highlighted for its clinical significance, function, and role in gastric cancer progression. By detecting MIEN1 copy number and expression level across eight gastric cancer cell lines and in tissue microarrays from 543 primary gastric cancer tissues, we found that MIEN1 amplification and overexpression correlated with sex and Lauren’s intestinal type classification of gastric cancer. Besides that, elevated MIEN1 expression was associated with poorer patient survival. In vitro experiments have shown that MIEN1 overexpression enhanced cell proliferation, invasion, and migration, whereas MIEN1 knockdown reversed these malignant phenotypes in vitro. Furthermore, MIEN1 knockdown inhibited tumorigenesis and metastasis of gastric cancer cells in nude mice. Mechanistically, MIEN1 activates the IL-6/JAK2/STAT3 signaling pathway, which drives the proliferation, invasion, and migration of gastric cancer cells. This study demonstrates that MIEN1 contributes to the malignant behavior of gastric cancer through the IL-6/JAK2/STAT3 pathway, suggesting that MIEN1 could serve as a valuable therapeutic target for gastric cancer.</description><subject>Amplification</subject><subject>Animals</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Chr17q12</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gene Amplification</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>IL-6/JAK2/STAT3</subject><subject>Interleukin-6 - genetics</subject><subject>Interleukin-6 - metabolism</subject><subject>Janus Kinase 2 - genetics</subject><subject>Janus Kinase 2 - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>MIEN1</subject><subject>Overexpression</subject><subject>Signal Transduction</subject><subject>STAT3 Transcription Factor - genetics</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Stomach Neoplasms - pathology</subject><issn>1357-2725</issn><issn>1878-5875</issn><issn>1878-5875</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1vEzEQhi0EoqXwDxDykcsm_livdy9IUVVoIMCBcLZm7dnE0X6kthPov6_LFo7MZUbvvDOjeQh5y9mCM14tD4vWTxb7hWCizFKV4xm55LWuC1Vr9TzXUulCaKEuyKsYD4wxroR8SS5kI0vJKnZJfn9d33zjdBpp2iPl-o4LCsOx9zZLHVjf-wQJ45_2AL3fjTAm2uIezn4KkU4d3UFMwVtqYbQY6NkDBZv8GZIfd3S9Karl59UXsfyxXW0lPULa_4L71-RFB33EN0_5ivz8eLO9vi023z-tr1ebwoqSp0K6Vru6VBU4sI5JYI2rnGq4E6jzE1aA68pOStVILVVZM4Gi7tqSgbS6QXlF3s97j2G6O2FMZvAxY-thxOkUjeScZ4JNI7K1nK02TDEG7Mwx-AHCveHMPDI3BzMzN4_Mzcw8j717unBqB3T_hv5CzoYPswHzn2ePwUTrMbNyPqBNxk3-_xceAHkbknc</recordid><startdate>202411</startdate><enddate>202411</enddate><creator>Lin, Jing</creator><creator>Wang, Dong</creator><creator>Zhou, Jiahui</creator><creator>Bai, Jing</creator><creator>Sun, Shouzhen</creator><creator>Jia, Xueyuan</creator><creator>Liang, Xiao</creator><creator>Fu, Songbin</creator><creator>Yu, Jingcui</creator><general>Elsevier Ltd</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>202411</creationdate><title>MIEN1 on the 17q12 amplicon facilitates the malignant behaviors of gastric cancer via activating IL-6/JAK2/STAT3 pathway</title><author>Lin, Jing ; Wang, Dong ; Zhou, Jiahui ; Bai, Jing ; Sun, Shouzhen ; Jia, Xueyuan ; Liang, Xiao ; Fu, Songbin ; Yu, Jingcui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c241t-3db7d8456adacd03a09d6d591d2e7343c2adf4f335937354802e28fb40a3c79e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Amplification</topic><topic>Animals</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Chr17q12</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Gene Amplification</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>IL-6/JAK2/STAT3</topic><topic>Interleukin-6 - genetics</topic><topic>Interleukin-6 - metabolism</topic><topic>Janus Kinase 2 - genetics</topic><topic>Janus Kinase 2 - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Middle Aged</topic><topic>MIEN1</topic><topic>Overexpression</topic><topic>Signal Transduction</topic><topic>STAT3 Transcription Factor - genetics</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - metabolism</topic><topic>Stomach Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Jing</creatorcontrib><creatorcontrib>Wang, Dong</creatorcontrib><creatorcontrib>Zhou, Jiahui</creatorcontrib><creatorcontrib>Bai, Jing</creatorcontrib><creatorcontrib>Sun, Shouzhen</creatorcontrib><creatorcontrib>Jia, Xueyuan</creatorcontrib><creatorcontrib>Liang, Xiao</creatorcontrib><creatorcontrib>Fu, Songbin</creatorcontrib><creatorcontrib>Yu, Jingcui</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>The international journal of biochemistry & cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Jing</au><au>Wang, Dong</au><au>Zhou, Jiahui</au><au>Bai, Jing</au><au>Sun, Shouzhen</au><au>Jia, Xueyuan</au><au>Liang, Xiao</au><au>Fu, Songbin</au><au>Yu, Jingcui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MIEN1 on the 17q12 amplicon facilitates the malignant behaviors of gastric cancer via activating IL-6/JAK2/STAT3 pathway</atitle><jtitle>The international journal of biochemistry & cell biology</jtitle><addtitle>Int J Biochem Cell Biol</addtitle><date>2024-11</date><risdate>2024</risdate><volume>176</volume><spage>106666</spage><pages>106666-</pages><artnum>106666</artnum><issn>1357-2725</issn><issn>1878-5875</issn><eissn>1878-5875</eissn><abstract>Oncogene amplification is a significant factor contributing to poor prognosis and limited treatment in patients with advanced gastric cancer. Therefore, identifying amplified oncogenes and elucidating their oncogenic mechanisms will provide reliable therapeutic targets for the clinical treatment of gastric cancer. In this study, we identify a high amplification of 17q12, which includes five oncogenes that are co-amplified and co-overexpressed with ERBB2 using array comparative genomic hybridization, with migration and invasion enhancer 1 (MIEN1) being particularly highlighted for its clinical significance, function, and role in gastric cancer progression. By detecting MIEN1 copy number and expression level across eight gastric cancer cell lines and in tissue microarrays from 543 primary gastric cancer tissues, we found that MIEN1 amplification and overexpression correlated with sex and Lauren’s intestinal type classification of gastric cancer. Besides that, elevated MIEN1 expression was associated with poorer patient survival. In vitro experiments have shown that MIEN1 overexpression enhanced cell proliferation, invasion, and migration, whereas MIEN1 knockdown reversed these malignant phenotypes in vitro. Furthermore, MIEN1 knockdown inhibited tumorigenesis and metastasis of gastric cancer cells in nude mice. Mechanistically, MIEN1 activates the IL-6/JAK2/STAT3 signaling pathway, which drives the proliferation, invasion, and migration of gastric cancer cells. This study demonstrates that MIEN1 contributes to the malignant behavior of gastric cancer through the IL-6/JAK2/STAT3 pathway, suggesting that MIEN1 could serve as a valuable therapeutic target for gastric cancer.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>39343060</pmid><doi>10.1016/j.biocel.2024.106666</doi></addata></record> |
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| subjects | Amplification Animals Cell Line, Tumor Cell Movement Cell Proliferation Chr17q12 Female Gastric cancer Gene Amplification Gene Expression Regulation, Neoplastic Humans IL-6/JAK2/STAT3 Interleukin-6 - genetics Interleukin-6 - metabolism Janus Kinase 2 - genetics Janus Kinase 2 - metabolism Male Mice Mice, Inbred BALB C Mice, Nude Middle Aged MIEN1 Overexpression Signal Transduction STAT3 Transcription Factor - genetics STAT3 Transcription Factor - metabolism Stomach Neoplasms - genetics Stomach Neoplasms - metabolism Stomach Neoplasms - pathology |
| title | MIEN1 on the 17q12 amplicon facilitates the malignant behaviors of gastric cancer via activating IL-6/JAK2/STAT3 pathway |
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