{"title":"METTL3 通过 m6A 修饰调控癌基因 Myc 的翻译，促进宫颈癌的发生和发展","authors":"Yanyan Ma, Hongyan Shi, Wei Zheng","doi":"10.24976/Discov.Med.202436188.176","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) is one of the major types of gynecological cancer, with a high global incidence and mortality rate. Methyltransferase-like 3 (METTL3), a key constituent of methyltransferase, plays a crucial role in various biological processes. Still, only a rare report has been made on its involvement in the progression of CC. Therefore, this study aims to investigate the impact of METTL3 in CC and its molecular mechanisms.</p><p><strong>Methods: </strong>Gene expression datasets about CC were obtained from the Gene Expression Omnibus (GEO) database, and the expression of <i>METTL3</i> and <i>Myc</i> was analyzed. Cell viability was detected after <i>METTL3</i> knockdown in HeLa and SiHa cells, followed by cell counting Kit-8 (CCK-8) assays. The relative expression of <i>METTL3</i> and <i>Myc</i> was detected via real-time quantitative PCR (qPCR) assays, and the protein expression was determined using Western blot. Meanwhile, cell invasion and migration capabilities were assessed utilizing transwell assays, and cell proliferation was detected using the EdU experiment. Furthermore, RNA methylation immunoprecipitation-qPCR detection was performed to determine the expression of <i>Myc</i> after N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification.</p><p><strong>Results: </strong>Analysis of the GEO database indicated elevated expression of METTL3 and Myc in CC tissues. Patients with high METTL3 expression had shorter disease-free survival, and patients with high Myc expression had shorter overall survival. Following the knockdown of <i>METTL3</i>, there was a significant reduction in the viability, proliferation, invasion, and migration abilities of HeLa and SiHa cells. Besides, the expression of <i>METTL3</i> and <i>Myc</i> mRNAs and proteins was greatly reduced. The level of m<sup>6</sup>A <i>Myc</i> decreased significantly after <i>METTL3</i> knockdown.</p><p><strong>Conclusions: </strong><i>METTL3</i> plays an important role in regulating cervical cancer cells. <i>METTL3</i> promotes CC development through m<sup>6</sup>A modification to regulate the expression of the oncogene <i>Myc</i>.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 188","pages":"1902-1910"},"PeriodicalIF":0.0000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"METTL3 Regulates the Translation of Oncogene Myc through m<sup>6</sup>A Modification and Promotes the Occurrence and Development of Cervical Cancer.\",\"authors\":\"Yanyan Ma, Hongyan Shi, Wei Zheng\",\"doi\":\"10.24976/Discov.Med.202436188.176\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cervical cancer (CC) is one of the major types of gynecological cancer, with a high global incidence and mortality rate. Methyltransferase-like 3 (METTL3), a key constituent of methyltransferase, plays a crucial role in various biological processes. Still, only a rare report has been made on its involvement in the progression of CC. Therefore, this study aims to investigate the impact of METTL3 in CC and its molecular mechanisms.</p><p><strong>Methods: </strong>Gene expression datasets about CC were obtained from the Gene Expression Omnibus (GEO) database, and the expression of <i>METTL3</i> and <i>Myc</i> was analyzed. Cell viability was detected after <i>METTL3</i> knockdown in HeLa and SiHa cells, followed by cell counting Kit-8 (CCK-8) assays. The relative expression of <i>METTL3</i> and <i>Myc</i> was detected via real-time quantitative PCR (qPCR) assays, and the protein expression was determined using Western blot. Meanwhile, cell invasion and migration capabilities were assessed utilizing transwell assays, and cell proliferation was detected using the EdU experiment. Furthermore, RNA methylation immunoprecipitation-qPCR detection was performed to determine the expression of <i>Myc</i> after N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification.</p><p><strong>Results: </strong>Analysis of the GEO database indicated elevated expression of METTL3 and Myc in CC tissues. Patients with high METTL3 expression had shorter disease-free survival, and patients with high Myc expression had shorter overall survival. Following the knockdown of <i>METTL3</i>, there was a significant reduction in the viability, proliferation, invasion, and migration abilities of HeLa and SiHa cells. Besides, the expression of <i>METTL3</i> and <i>Myc</i> mRNAs and proteins was greatly reduced. The level of m<sup>6</sup>A <i>Myc</i> decreased significantly after <i>METTL3</i> knockdown.</p><p><strong>Conclusions: </strong><i>METTL3</i> plays an important role in regulating cervical cancer cells. <i>METTL3</i> promotes CC development through m<sup>6</sup>A modification to regulate the expression of the oncogene <i>Myc</i>.</p>\",\"PeriodicalId\":93980,\"journal\":{\"name\":\"Discovery medicine\",\"volume\":\"36 188\",\"pages\":\"1902-1910\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Discovery medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.24976/Discov.Med.202436188.176\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Discovery medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.24976/Discov.Med.202436188.176","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
背景：宫颈癌（CC）是妇科癌症的主要类型之一，在全球的发病率和死亡率都很高。甲基转移酶样 3（METTL3）是甲基转移酶的关键成分，在各种生物过程中发挥着至关重要的作用。然而，关于它参与CC进展的报道还很少见。因此，本研究旨在探讨 METTL3 在 CC 中的影响及其分子机制：方法：从基因表达总库（GEO）数据库中获取有关 CC 的基因表达数据集，分析 METTL3 和 Myc 的表达。在HeLa和SiHa细胞中敲除METTL3后，用细胞计数试剂盒-8（CCK-8）检测细胞活力。通过实时定量 PCR（qPCR）检测 METTL3 和 Myc 的相对表达，并通过 Western 印迹检测蛋白表达。同时，细胞侵袭和迁移能力的评估采用了透孔实验，细胞增殖的检测采用了 EdU 实验。此外，还进行了 RNA 甲基化免疫沉淀-qPCR 检测，以确定 N6-甲基腺苷（m6A）修饰后 Myc 的表达情况：结果：对GEO数据库的分析表明，METTL3和Myc在CC组织中的表达量升高。METTL3高表达的患者无病生存期较短，Myc高表达的患者总生存期较短。敲除 METTL3 后，HeLa 和 SiHa 细胞的活力、增殖、侵袭和迁移能力显著下降。此外，METTL3和Myc mRNA及蛋白的表达也大大减少。结论：METTL3对HeLa和SiHa细胞的增殖、侵袭和迁移能力有重要作用：结论：METTL3在宫颈癌细胞调控中发挥着重要作用。结论：METTL3在宫颈癌细胞的调控过程中发挥着重要作用。METTL3通过m6A修饰来调控癌基因Myc的表达，从而促进宫颈癌的发展。
METTL3 Regulates the Translation of Oncogene Myc through m6A Modification and Promotes the Occurrence and Development of Cervical Cancer.
Background: Cervical cancer (CC) is one of the major types of gynecological cancer, with a high global incidence and mortality rate. Methyltransferase-like 3 (METTL3), a key constituent of methyltransferase, plays a crucial role in various biological processes. Still, only a rare report has been made on its involvement in the progression of CC. Therefore, this study aims to investigate the impact of METTL3 in CC and its molecular mechanisms.
Methods: Gene expression datasets about CC were obtained from the Gene Expression Omnibus (GEO) database, and the expression of METTL3 and Myc was analyzed. Cell viability was detected after METTL3 knockdown in HeLa and SiHa cells, followed by cell counting Kit-8 (CCK-8) assays. The relative expression of METTL3 and Myc was detected via real-time quantitative PCR (qPCR) assays, and the protein expression was determined using Western blot. Meanwhile, cell invasion and migration capabilities were assessed utilizing transwell assays, and cell proliferation was detected using the EdU experiment. Furthermore, RNA methylation immunoprecipitation-qPCR detection was performed to determine the expression of Myc after N6-methyladenosine (m6A) modification.
Results: Analysis of the GEO database indicated elevated expression of METTL3 and Myc in CC tissues. Patients with high METTL3 expression had shorter disease-free survival, and patients with high Myc expression had shorter overall survival. Following the knockdown of METTL3, there was a significant reduction in the viability, proliferation, invasion, and migration abilities of HeLa and SiHa cells. Besides, the expression of METTL3 and Myc mRNAs and proteins was greatly reduced. The level of m6A Myc decreased significantly after METTL3 knockdown.
Conclusions: METTL3 plays an important role in regulating cervical cancer cells. METTL3 promotes CC development through m6A modification to regulate the expression of the oncogene Myc.
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