Long non‐coding RNA MIF‐AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4
Long non‐coding RNA MIF‐AS1 (lncMIF‐AS1) has been found to be upregulated in the tumor tissues of gastric cancer; however, its importance for the progression of gastric cancer remains unknown. Thus, the present study was designed to determine the role of the lncMIF‐AS1‐based signal transduction path...
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| Veröffentlicht in: | Cancer science 2018-12, Vol.109 (12), p.3714-3725 |
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| creator | Li, Linhai Li, Yuejin Huang, Yingguang Ouyang, Yiming Zhu, Yu Wang, Yongzhi Guo, Xiaodong Yuan, Ying Gong, Kunmei |
| description | Long non‐coding RNA MIF‐AS1 (lncMIF‐AS1) has been found to be upregulated in the tumor tissues of gastric cancer; however, its importance for the progression of gastric cancer remains unknown. Thus, the present study was designed to determine the role of the lncMIF‐AS1‐based signal transduction pathway in mediating the proliferation and apoptosis of gastric cancer cells. Differentially expressed lncRNAs and mRNAs were screened out using microarray analysis, based on the published data (GSE63288), and validated using quantitative RT‐PCR. Target relationships between lncRNA‐micro RNA (miRNA) and miRNA‐mRNA were predicted by bioinformatics analysis and verified by dual‐luciferase reporter assay. Protein expression of NDUFA4, COX6C and COX5B was detected by western blot. Cell proliferation, cell cycle and apoptosis were determined using colony formation assay and flow cytometry analysis. Oxidative phosphorylation in gastric cancer cells was assessed by levels of oxygen consumption and ATP synthase activity. Expression of lncMIF‐AS1 and NDUFA4 were upregulated in gastric cancer tissues and cells as compared with non‐cancerous gastric tissues and cells (P |
| doi_str_mv | 10.1111/cas.13801 |
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Our findings showed that lncMIF‐AS1 is involved in gastric cancer tumorigenesis as a tumor activator gene. Through upregulation of NDUFA4, lncMIF‐AS1 promotes gastric cancer cell proliferation and repressed apoptosis. Moreover, we showed that lncMIF‐AS1 activates NDUFA4 expression by sponging to miR‐212‐5p in gastric cancer cells. And inhibition of lnvMIF‐AS1/miR‐212‐5p/NDUFA4 may provide an attractive therapeutic target for the treatment of gastric cancer.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.13801</identifier><identifier>PMID: 30238562</identifier><language>eng</language><publisher>England: John Wiley and Sons Inc</publisher><subject>3' Untranslated Regions ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Databases, Genetic ; Down-Regulation ; Electron Transport Complex IV - genetics ; gastric cancer ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; lncMIF‐AS1 ; MicroRNAs - genetics ; miR‐212‐5p ; NDUFA4 ; Oligonucleotide Array Sequence Analysis ; Original ; Oxidative Phosphorylation ; RNA, Long Noncoding - genetics ; Stomach Neoplasms - genetics</subject><ispartof>Cancer science, 2018-12, Vol.109 (12), p.3714-3725</ispartof><rights>2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-4468-5801</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272088/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272088/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30238562$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Linhai</creatorcontrib><creatorcontrib>Li, Yuejin</creatorcontrib><creatorcontrib>Huang, Yingguang</creatorcontrib><creatorcontrib>Ouyang, Yiming</creatorcontrib><creatorcontrib>Zhu, Yu</creatorcontrib><creatorcontrib>Wang, Yongzhi</creatorcontrib><creatorcontrib>Guo, Xiaodong</creatorcontrib><creatorcontrib>Yuan, Ying</creatorcontrib><creatorcontrib>Gong, Kunmei</creatorcontrib><title>Long non‐coding RNA MIF‐AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Long non‐coding RNA MIF‐AS1 (lncMIF‐AS1) has been found to be upregulated in the tumor tissues of gastric cancer; however, its importance for the progression of gastric cancer remains unknown. Thus, the present study was designed to determine the role of the lncMIF‐AS1‐based signal transduction pathway in mediating the proliferation and apoptosis of gastric cancer cells. Differentially expressed lncRNAs and mRNAs were screened out using microarray analysis, based on the published data (GSE63288), and validated using quantitative RT‐PCR. Target relationships between lncRNA‐micro RNA (miRNA) and miRNA‐mRNA were predicted by bioinformatics analysis and verified by dual‐luciferase reporter assay. Protein expression of NDUFA4, COX6C and COX5B was detected by western blot. Cell proliferation, cell cycle and apoptosis were determined using colony formation assay and flow cytometry analysis. Oxidative phosphorylation in gastric cancer cells was assessed by levels of oxygen consumption and ATP synthase activity. Expression of lncMIF‐AS1 and NDUFA4 were upregulated in gastric cancer tissues and cells as compared with non‐cancerous gastric tissues and cells (P < .05). MiR‐212‐5p was identified as the most important miRNA linker between lncMIF‐AS1 and NDUFA4, which was negatively regulated by lncMIF‐AS1 and its depletion is the main cause of NDUFA4 overexpression (P < .01). The upregulated expression of NDUFA4 then greatly promoted the proliferation and decreased the apoptosis of gastric cancer cells through activation of the oxidative phosphorylation pathway. Taken together, the present study implies that inhibition of lncMIF‐AS1/miR‐212‐5p/NDUFA4 signal transduction may provide a promising therapeutic target for the treatment of gastric cancer.
Our findings showed that lncMIF‐AS1 is involved in gastric cancer tumorigenesis as a tumor activator gene. Through upregulation of NDUFA4, lncMIF‐AS1 promotes gastric cancer cell proliferation and repressed apoptosis. Moreover, we showed that lncMIF‐AS1 activates NDUFA4 expression by sponging to miR‐212‐5p in gastric cancer cells. And inhibition of lnvMIF‐AS1/miR‐212‐5p/NDUFA4 may provide an attractive therapeutic target for the treatment of gastric cancer.</description><subject>3' Untranslated Regions</subject><subject>Apoptosis</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Databases, Genetic</subject><subject>Down-Regulation</subject><subject>Electron Transport Complex IV - genetics</subject><subject>gastric cancer</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>lncMIF‐AS1</subject><subject>MicroRNAs - genetics</subject><subject>miR‐212‐5p</subject><subject>NDUFA4</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Original</subject><subject>Oxidative Phosphorylation</subject><subject>RNA, Long Noncoding - genetics</subject><subject>Stomach Neoplasms - genetics</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNpVUctO3DAUtRCoPNoFP4C8ZBPwI3GcDdJo6LRIA5WgrC3HuRmMMnawk6LZ8Qn9Rr6kDi9Rb3yvz9E51-cidEjJCU3n1Oh4QrkkdAvtUZ5XWUmI2H6py6winO2i_RjvCeEir_IvaJcTxmUh2B4al96tsPPu-emv8Y1NzfXVDF9eLNLD7IbiPvi1HyDilY5DsAYb7QwEbKDrJrCzLQQ9WO-wdg0O0IwmsXXv-8FHG_Hg8dgHWI2dHgBfnd8uZvlXtNPqLsK3t_sA3S6-_57_zJa_flzMZ8vsnleCZtKwuhQVLYHQWtYAvOCCCqElqavGMNAFK7WueVHmbVGzxrSVlI2RxpSkLSg_QGevuv1Yr6Ex4IagO9UHu9Zho7y26n_E2Tu18n-UYCUjUiaB4zeB4B9GiINa2zh9XTvwY1Rsyj9PI7JEPfrs9WHynnUinL4SHm0Hmw-cEjWJqLRE9bJENU-5TwX_B88Vkgo</recordid><startdate>201812</startdate><enddate>201812</enddate><creator>Li, Linhai</creator><creator>Li, Yuejin</creator><creator>Huang, Yingguang</creator><creator>Ouyang, Yiming</creator><creator>Zhu, Yu</creator><creator>Wang, Yongzhi</creator><creator>Guo, Xiaodong</creator><creator>Yuan, Ying</creator><creator>Gong, Kunmei</creator><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4468-5801</orcidid></search><sort><creationdate>201812</creationdate><title>Long non‐coding RNA MIF‐AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4</title><author>Li, Linhai ; Li, Yuejin ; Huang, Yingguang ; Ouyang, Yiming ; Zhu, Yu ; Wang, Yongzhi ; Guo, Xiaodong ; Yuan, Ying ; Gong, Kunmei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j3961-8c2b76917e01b8bee3536166a80b9dc2ea527aab3574f5b2dcf988dc8cc70f513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>3' Untranslated Regions</topic><topic>Apoptosis</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Databases, Genetic</topic><topic>Down-Regulation</topic><topic>Electron Transport Complex IV - genetics</topic><topic>gastric cancer</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>lncMIF‐AS1</topic><topic>MicroRNAs - genetics</topic><topic>miR‐212‐5p</topic><topic>NDUFA4</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Original</topic><topic>Oxidative Phosphorylation</topic><topic>RNA, Long Noncoding - genetics</topic><topic>Stomach Neoplasms - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Linhai</creatorcontrib><creatorcontrib>Li, Yuejin</creatorcontrib><creatorcontrib>Huang, Yingguang</creatorcontrib><creatorcontrib>Ouyang, Yiming</creatorcontrib><creatorcontrib>Zhu, Yu</creatorcontrib><creatorcontrib>Wang, Yongzhi</creatorcontrib><creatorcontrib>Guo, Xiaodong</creatorcontrib><creatorcontrib>Yuan, Ying</creatorcontrib><creatorcontrib>Gong, Kunmei</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Linhai</au><au>Li, Yuejin</au><au>Huang, Yingguang</au><au>Ouyang, Yiming</au><au>Zhu, Yu</au><au>Wang, Yongzhi</au><au>Guo, Xiaodong</au><au>Yuan, Ying</au><au>Gong, Kunmei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long non‐coding RNA MIF‐AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2018-12</date><risdate>2018</risdate><volume>109</volume><issue>12</issue><spage>3714</spage><epage>3725</epage><pages>3714-3725</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Long non‐coding RNA MIF‐AS1 (lncMIF‐AS1) has been found to be upregulated in the tumor tissues of gastric cancer; however, its importance for the progression of gastric cancer remains unknown. Thus, the present study was designed to determine the role of the lncMIF‐AS1‐based signal transduction pathway in mediating the proliferation and apoptosis of gastric cancer cells. Differentially expressed lncRNAs and mRNAs were screened out using microarray analysis, based on the published data (GSE63288), and validated using quantitative RT‐PCR. Target relationships between lncRNA‐micro RNA (miRNA) and miRNA‐mRNA were predicted by bioinformatics analysis and verified by dual‐luciferase reporter assay. Protein expression of NDUFA4, COX6C and COX5B was detected by western blot. Cell proliferation, cell cycle and apoptosis were determined using colony formation assay and flow cytometry analysis. Oxidative phosphorylation in gastric cancer cells was assessed by levels of oxygen consumption and ATP synthase activity. Expression of lncMIF‐AS1 and NDUFA4 were upregulated in gastric cancer tissues and cells as compared with non‐cancerous gastric tissues and cells (P < .05). MiR‐212‐5p was identified as the most important miRNA linker between lncMIF‐AS1 and NDUFA4, which was negatively regulated by lncMIF‐AS1 and its depletion is the main cause of NDUFA4 overexpression (P < .01). The upregulated expression of NDUFA4 then greatly promoted the proliferation and decreased the apoptosis of gastric cancer cells through activation of the oxidative phosphorylation pathway. Taken together, the present study implies that inhibition of lncMIF‐AS1/miR‐212‐5p/NDUFA4 signal transduction may provide a promising therapeutic target for the treatment of gastric cancer.
Our findings showed that lncMIF‐AS1 is involved in gastric cancer tumorigenesis as a tumor activator gene. Through upregulation of NDUFA4, lncMIF‐AS1 promotes gastric cancer cell proliferation and repressed apoptosis. Moreover, we showed that lncMIF‐AS1 activates NDUFA4 expression by sponging to miR‐212‐5p in gastric cancer cells. And inhibition of lnvMIF‐AS1/miR‐212‐5p/NDUFA4 may provide an attractive therapeutic target for the treatment of gastric cancer.</abstract><cop>England</cop><pub>John Wiley and Sons Inc</pub><pmid>30238562</pmid><doi>10.1111/cas.13801</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-4468-5801</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 3' Untranslated Regions Apoptosis Cell Line, Tumor Cell Proliferation Databases, Genetic Down-Regulation Electron Transport Complex IV - genetics gastric cancer Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans lncMIF‐AS1 MicroRNAs - genetics miR‐212‐5p NDUFA4 Oligonucleotide Array Sequence Analysis Original Oxidative Phosphorylation RNA, Long Noncoding - genetics Stomach Neoplasms - genetics |
| title | Long non‐coding RNA MIF‐AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4 |
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