{"title":"METTL3/MALAT1/ELAVL1轴促进卵巢癌的肿瘤生长","authors":"Jian Xiong, Wenqin Lian, Rui Zhao, Kefei Gao","doi":"10.2147/OTT.S431810","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Studies increasingly recognize the role of N6-methyladenosine (<i>m6A</i>) modification in cancer occurrence and development. METTL3 is a core catalytic subunit of m6A-modified methyltransferases complex, but its regulatory mechanism in ovarian cancer (OC) is not clear.</p><p><strong>Methods: </strong>In this study, GEPIA 2.0 database was applied for expression analysis, survival analysis and correlation analysis for OC. Additionally, in vitro and in vivo assays were conducted to explore regulatory mechanisms of METTL3 in OC.</p><p><strong>Results: </strong>We found that METTL3 and <i>MALAT1</i> were significantly overexpressed in OC tissues and cells compared to normal ovarian tissues and cells. The proliferation rate of OC cells was reduced significantly after knocking down the expression of <i>METTL3</i> or <i>MALAT1</i>. Subsequently, <i>MALAT1</i> as oncogene was found to interact with METTL3 and was upregulated in OC tissues and cells. Silencing <i>MALAT1</i> inhibited OC cell proliferation. Further studies indicated that METTL3 enhanced the stability of <i>MALAT1</i> by promoting the m6A modification of <i>MALAT1</i> and that ELAVL1 as a downstream binding protein significantly up-regulated <i>MALAT1</i> expression.</p><p><strong>Conclusion: </strong>In conclusion, METTL3 was a carcinogenic molecule that promoted the occurrence of OC. The potential mechanism of the carcinogenic effect of METTL3 was realized by enhancing the m6A modification of <i>MALAT1</i> mRNA through RNA binding protein ELAVL1.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860502/pdf/","citationCount":"0","resultStr":"{\"title\":\"METTL3/<i>MALAT1</i>/ELAVL1 Axis Promotes Tumor Growth in Ovarian Cancer.\",\"authors\":\"Jian Xiong, Wenqin Lian, Rui Zhao, Kefei Gao\",\"doi\":\"10.2147/OTT.S431810\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Studies increasingly recognize the role of N6-methyladenosine (<i>m6A</i>) modification in cancer occurrence and development. METTL3 is a core catalytic subunit of m6A-modified methyltransferases complex, but its regulatory mechanism in ovarian cancer (OC) is not clear.</p><p><strong>Methods: </strong>In this study, GEPIA 2.0 database was applied for expression analysis, survival analysis and correlation analysis for OC. Additionally, in vitro and in vivo assays were conducted to explore regulatory mechanisms of METTL3 in OC.</p><p><strong>Results: </strong>We found that METTL3 and <i>MALAT1</i> were significantly overexpressed in OC tissues and cells compared to normal ovarian tissues and cells. The proliferation rate of OC cells was reduced significantly after knocking down the expression of <i>METTL3</i> or <i>MALAT1</i>. Subsequently, <i>MALAT1</i> as oncogene was found to interact with METTL3 and was upregulated in OC tissues and cells. Silencing <i>MALAT1</i> inhibited OC cell proliferation. Further studies indicated that METTL3 enhanced the stability of <i>MALAT1</i> by promoting the m6A modification of <i>MALAT1</i> and that ELAVL1 as a downstream binding protein significantly up-regulated <i>MALAT1</i> expression.</p><p><strong>Conclusion: </strong>In conclusion, METTL3 was a carcinogenic molecule that promoted the occurrence of OC. The potential mechanism of the carcinogenic effect of METTL3 was realized by enhancing the m6A modification of <i>MALAT1</i> mRNA through RNA binding protein ELAVL1.</p>\",\"PeriodicalId\":19534,\"journal\":{\"name\":\"OncoTargets and therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-02-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860502/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"OncoTargets and therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/OTT.S431810\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"OncoTargets and therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/OTT.S431810","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
METTL3/MALAT1/ELAVL1 Axis Promotes Tumor Growth in Ovarian Cancer.
Background: Studies increasingly recognize the role of N6-methyladenosine (m6A) modification in cancer occurrence and development. METTL3 is a core catalytic subunit of m6A-modified methyltransferases complex, but its regulatory mechanism in ovarian cancer (OC) is not clear.
Methods: In this study, GEPIA 2.0 database was applied for expression analysis, survival analysis and correlation analysis for OC. Additionally, in vitro and in vivo assays were conducted to explore regulatory mechanisms of METTL3 in OC.
Results: We found that METTL3 and MALAT1 were significantly overexpressed in OC tissues and cells compared to normal ovarian tissues and cells. The proliferation rate of OC cells was reduced significantly after knocking down the expression of METTL3 or MALAT1. Subsequently, MALAT1 as oncogene was found to interact with METTL3 and was upregulated in OC tissues and cells. Silencing MALAT1 inhibited OC cell proliferation. Further studies indicated that METTL3 enhanced the stability of MALAT1 by promoting the m6A modification of MALAT1 and that ELAVL1 as a downstream binding protein significantly up-regulated MALAT1 expression.
Conclusion: In conclusion, METTL3 was a carcinogenic molecule that promoted the occurrence of OC. The potential mechanism of the carcinogenic effect of METTL3 was realized by enhancing the m6A modification of MALAT1 mRNA through RNA binding protein ELAVL1.
期刊介绍：
OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer.
The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype.
Specific topics covered by the journal include:
-Novel therapeutic targets and innovative agents
-Novel therapeutic regimens for improved benefit and/or decreased side effects
-Early stage clinical trials
Further considerations when submitting to OncoTargets and Therapy:
-Studies containing in vivo animal model data will be considered favorably.
-Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines.
-Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples.
-Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up.
-Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up.
-Single nucleotide polymorphism (SNP) studies will not be considered.
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