Next-Generation Sequencing Analysis of mRNA Profile in Cisplatin-Resistant Gastric Cancer Cell Line SGC7901

BACKGROUND Cisplatin-resistant gastric cancer (GC) occurs in patients with GC treated with cisplatin-based chemotherapy, which results in disease progression and early recurrence during the treatment. MATERIAL AND METHODS To understand the initiation and developmental mechanism underlying cisplatin-...

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Veröffentlicht in:Medical science monitor 2019-04, Vol.25, p.2386-2396
Hauptverfasser: Deng, Zhenwei, Wang, Huaiming, Guo, Guohu, Li, Xiyao, Cai, Yongchang, Tang, Yuxin, Wang, Yijun, Li, Jiabao, Lu, Zhibin, Yu, Xueqiao, Li, Ruiping, Li, Libo
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container_title Medical science monitor
container_volume 25
creator Deng, Zhenwei
Wang, Huaiming
Guo, Guohu
Li, Xiyao
Cai, Yongchang
Tang, Yuxin
Wang, Yijun
Li, Jiabao
Lu, Zhibin
Yu, Xueqiao
Li, Ruiping
Li, Libo
description BACKGROUND Cisplatin-resistant gastric cancer (GC) occurs in patients with GC treated with cisplatin-based chemotherapy, which results in disease progression and early recurrence during the treatment. MATERIAL AND METHODS To understand the initiation and developmental mechanism underlying cisplatin-resistant GC, we developed cisplatin-resistant SGC7901 cells (SGC7901/DDP) from the parental cells (SGC7901/S) by continuous exposure to increasing concentrations of cisplatin and subjected these 2 cell lines to RNA sequencing analysis. The data were verified by quantitative polymerase chain reaction and their functional role was evaluated by cell counting kit 8 assay and cell apoptosis and cell cycle flow cytometric analysis. Bioinformatics analysis was performed to classify the differentially-expressed genes (DEGs) involved in the development of cisplatin resistance. RESULTS In comparison with SGC7901/S cells, SGC7901/DDP cells showed a total of 3165 DEGs (2014 upregulated and 1151 downregulated, fold change ≥2, and adjusted P value
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MATERIAL AND METHODS To understand the initiation and developmental mechanism underlying cisplatin-resistant GC, we developed cisplatin-resistant SGC7901 cells (SGC7901/DDP) from the parental cells (SGC7901/S) by continuous exposure to increasing concentrations of cisplatin and subjected these 2 cell lines to RNA sequencing analysis. The data were verified by quantitative polymerase chain reaction and their functional role was evaluated by cell counting kit 8 assay and cell apoptosis and cell cycle flow cytometric analysis. Bioinformatics analysis was performed to classify the differentially-expressed genes (DEGs) involved in the development of cisplatin resistance. RESULTS In comparison with SGC7901/S cells, SGC7901/DDP cells showed a total of 3165 DEGs (2014 upregulated and 1151 downregulated, fold change ≥2, and adjusted P value &lt;0.001). qRT-PCR confirmed the reliability of the RNA sequencing results. Depletion of the top 5 upregulated mRNAs reversed the resistant index, increased apoptotic SGC7901/DDP cells, and arrested the cells at G2/M phase. Gene ontology analysis revealed that the DEGs mainly regulate metabolic process, immune system, locomotion, cell adhesion, cell growth, cell death, cytoskeleton organization, cell binding, signal transducing activity, and antioxidant activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs were mainly involved in the PI3K-Akt signaling pathway, Rap1 signaling pathway, proteoglycans in cancer, regulation of actin cytoskeleton, and pathways in cancer. CONCLUSIONS The present study is the first to interrogate mRNAs profiles in human GC cells with cisplatin resistance using RNA sequencing, which may assist in discovering potential therapeutic targets for cisplatin-resistant GC patients.</description><identifier>ISSN: 1643-3750</identifier><identifier>ISSN: 1234-1010</identifier><identifier>EISSN: 1643-3750</identifier><identifier>DOI: 10.12659/MSM.915866</identifier><identifier>PMID: 30938333</identifier><language>eng</language><publisher>United States: International Scientific Literature, Inc</publisher><subject>Lab/In Vitro Research</subject><ispartof>Medical science monitor, 2019-04, Vol.25, p.2386-2396</ispartof><rights>Med Sci Monit, 2019 2019</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-291bf33a6976738409afa0efe14141de1ddfcdfac94f9ffff1d74edb3eca96483</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457324/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457324/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27907,27908,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30938333$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Deng, Zhenwei</creatorcontrib><creatorcontrib>Wang, Huaiming</creatorcontrib><creatorcontrib>Guo, Guohu</creatorcontrib><creatorcontrib>Li, Xiyao</creatorcontrib><creatorcontrib>Cai, Yongchang</creatorcontrib><creatorcontrib>Tang, Yuxin</creatorcontrib><creatorcontrib>Wang, Yijun</creatorcontrib><creatorcontrib>Li, Jiabao</creatorcontrib><creatorcontrib>Lu, Zhibin</creatorcontrib><creatorcontrib>Yu, Xueqiao</creatorcontrib><creatorcontrib>Li, Ruiping</creatorcontrib><creatorcontrib>Li, Libo</creatorcontrib><title>Next-Generation Sequencing Analysis of mRNA Profile in Cisplatin-Resistant Gastric Cancer Cell Line SGC7901</title><title>Medical science monitor</title><addtitle>Med Sci Monit</addtitle><description>BACKGROUND Cisplatin-resistant gastric cancer (GC) occurs in patients with GC treated with cisplatin-based chemotherapy, which results in disease progression and early recurrence during the treatment. MATERIAL AND METHODS To understand the initiation and developmental mechanism underlying cisplatin-resistant GC, we developed cisplatin-resistant SGC7901 cells (SGC7901/DDP) from the parental cells (SGC7901/S) by continuous exposure to increasing concentrations of cisplatin and subjected these 2 cell lines to RNA sequencing analysis. The data were verified by quantitative polymerase chain reaction and their functional role was evaluated by cell counting kit 8 assay and cell apoptosis and cell cycle flow cytometric analysis. Bioinformatics analysis was performed to classify the differentially-expressed genes (DEGs) involved in the development of cisplatin resistance. RESULTS In comparison with SGC7901/S cells, SGC7901/DDP cells showed a total of 3165 DEGs (2014 upregulated and 1151 downregulated, fold change ≥2, and adjusted P value &lt;0.001). qRT-PCR confirmed the reliability of the RNA sequencing results. Depletion of the top 5 upregulated mRNAs reversed the resistant index, increased apoptotic SGC7901/DDP cells, and arrested the cells at G2/M phase. Gene ontology analysis revealed that the DEGs mainly regulate metabolic process, immune system, locomotion, cell adhesion, cell growth, cell death, cytoskeleton organization, cell binding, signal transducing activity, and antioxidant activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs were mainly involved in the PI3K-Akt signaling pathway, Rap1 signaling pathway, proteoglycans in cancer, regulation of actin cytoskeleton, and pathways in cancer. CONCLUSIONS The present study is the first to interrogate mRNAs profiles in human GC cells with cisplatin resistance using RNA sequencing, which may assist in discovering potential therapeutic targets for cisplatin-resistant GC patients.</description><subject>Lab/In Vitro Research</subject><issn>1643-3750</issn><issn>1234-1010</issn><issn>1643-3750</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpVkNFLwzAQxoMoTqdPvkvepTNp0rR5EUbRKmxTNn0uWXqZ0S6dSSfuv7c4HfPu4Q7u-76DH0IXlAxoLBJ5PZ6NB5ImmRAH6IQKziKWJuRwb--h0xDeCIkzQZJj1GNEsowxdoLeJ_DVRgU48Kq1jcMz-FiD09Yt8NCpehNswI3By-lkiJ98Y2wN2Dqc27CqO4eLptBJWuVaXKjQeqtxrpwGj3OoazyyDvCsyFNJ6Bk6MqoOcP47--jl7vY5v49Gj8VDPhxFmsesjWJJ54YxJWQqUpZxIpVRBAxQ3nUFtKqMrozSkhtpuqJVyqGaM9BKCp6xPrrZ5q7W8yVUGlzrVV2uvF0qvykbZcv_F2dfy0XzWQqepCzmXcDVNkD7JgQPZuelpPxhXnbMyy3zTn25_26n_YPMvgFzxH62</recordid><startdate>20190402</startdate><enddate>20190402</enddate><creator>Deng, Zhenwei</creator><creator>Wang, Huaiming</creator><creator>Guo, Guohu</creator><creator>Li, Xiyao</creator><creator>Cai, Yongchang</creator><creator>Tang, Yuxin</creator><creator>Wang, Yijun</creator><creator>Li, Jiabao</creator><creator>Lu, Zhibin</creator><creator>Yu, Xueqiao</creator><creator>Li, Ruiping</creator><creator>Li, Libo</creator><general>International Scientific Literature, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20190402</creationdate><title>Next-Generation Sequencing Analysis of mRNA Profile in Cisplatin-Resistant Gastric Cancer Cell Line SGC7901</title><author>Deng, Zhenwei ; Wang, Huaiming ; Guo, Guohu ; Li, Xiyao ; Cai, Yongchang ; Tang, Yuxin ; Wang, Yijun ; Li, Jiabao ; Lu, Zhibin ; Yu, Xueqiao ; Li, Ruiping ; Li, Libo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-291bf33a6976738409afa0efe14141de1ddfcdfac94f9ffff1d74edb3eca96483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Lab/In Vitro Research</topic><toplevel>online_resources</toplevel><creatorcontrib>Deng, Zhenwei</creatorcontrib><creatorcontrib>Wang, Huaiming</creatorcontrib><creatorcontrib>Guo, Guohu</creatorcontrib><creatorcontrib>Li, Xiyao</creatorcontrib><creatorcontrib>Cai, Yongchang</creatorcontrib><creatorcontrib>Tang, Yuxin</creatorcontrib><creatorcontrib>Wang, Yijun</creatorcontrib><creatorcontrib>Li, Jiabao</creatorcontrib><creatorcontrib>Lu, Zhibin</creatorcontrib><creatorcontrib>Yu, Xueqiao</creatorcontrib><creatorcontrib>Li, Ruiping</creatorcontrib><creatorcontrib>Li, Libo</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Medical science monitor</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Deng, Zhenwei</au><au>Wang, Huaiming</au><au>Guo, Guohu</au><au>Li, Xiyao</au><au>Cai, Yongchang</au><au>Tang, Yuxin</au><au>Wang, Yijun</au><au>Li, Jiabao</au><au>Lu, Zhibin</au><au>Yu, Xueqiao</au><au>Li, Ruiping</au><au>Li, Libo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Next-Generation Sequencing Analysis of mRNA Profile in Cisplatin-Resistant Gastric Cancer Cell Line SGC7901</atitle><jtitle>Medical science monitor</jtitle><addtitle>Med Sci Monit</addtitle><date>2019-04-02</date><risdate>2019</risdate><volume>25</volume><spage>2386</spage><epage>2396</epage><pages>2386-2396</pages><issn>1643-3750</issn><issn>1234-1010</issn><eissn>1643-3750</eissn><abstract>BACKGROUND Cisplatin-resistant gastric cancer (GC) occurs in patients with GC treated with cisplatin-based chemotherapy, which results in disease progression and early recurrence during the treatment. MATERIAL AND METHODS To understand the initiation and developmental mechanism underlying cisplatin-resistant GC, we developed cisplatin-resistant SGC7901 cells (SGC7901/DDP) from the parental cells (SGC7901/S) by continuous exposure to increasing concentrations of cisplatin and subjected these 2 cell lines to RNA sequencing analysis. The data were verified by quantitative polymerase chain reaction and their functional role was evaluated by cell counting kit 8 assay and cell apoptosis and cell cycle flow cytometric analysis. Bioinformatics analysis was performed to classify the differentially-expressed genes (DEGs) involved in the development of cisplatin resistance. RESULTS In comparison with SGC7901/S cells, SGC7901/DDP cells showed a total of 3165 DEGs (2014 upregulated and 1151 downregulated, fold change ≥2, and adjusted P value &lt;0.001). qRT-PCR confirmed the reliability of the RNA sequencing results. Depletion of the top 5 upregulated mRNAs reversed the resistant index, increased apoptotic SGC7901/DDP cells, and arrested the cells at G2/M phase. Gene ontology analysis revealed that the DEGs mainly regulate metabolic process, immune system, locomotion, cell adhesion, cell growth, cell death, cytoskeleton organization, cell binding, signal transducing activity, and antioxidant activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs were mainly involved in the PI3K-Akt signaling pathway, Rap1 signaling pathway, proteoglycans in cancer, regulation of actin cytoskeleton, and pathways in cancer. 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title Next-Generation Sequencing Analysis of mRNA Profile in Cisplatin-Resistant Gastric Cancer Cell Line SGC7901
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