{"title":"METTL3调控PODN的m6A甲基化与索拉非尼协同在甲状腺乳头状癌中表现出抗肿瘤功能","authors":"Yanlei Sun, Bolu Sun, Mei Yang, Qiangqun Deng","doi":"10.1007/s10528-025-11201-4","DOIUrl":null,"url":null,"abstract":"<p><p>Podocan (PODN) has strong clinical diagnostic significance, and sorafenib is a versatile anti-cancer drug. Yet, neither the individual nor combined effects of PODN and sorafenib on papillary thyroid carcinoma (PTC) malignancy, nor their mechanisms, have been reported. We employed bioinformatics to pinpoint mRNAs significantly downregulated in PTC that negatively affected tumor cell migration. Using qRT-PCR, we quantified PODN and Methyltransferase-like 3 (METTL3) levels in PTC samples. MeRIP, Pearson analysis, and RIP assays validated regulatory links among PODN, METTL3, and IGF2BP1. We treated PTC cells with sorafenib or induced PODN overexpression, then assessed proliferation, migration, and invasion via CCK-8, wound healing, and Transwell assays. Both PODN and METTL3 showed low expression in PTC samples and correlated positively. Sorafenib or high PODN levels suppressed PTC cell survival, migration, and invasion. Elevated PODN also amplified sorafenib's antitumor effects in PTC cells. Moreover, METTL3 increased N6-methyladenosine (m<sup>6</sup>A) methylation of PODN, upregulating PODN mRNA and protein via an IGF2BP1-dependent mechanism. Our findings indicate that PODN inhibits PTC cell invasion, migration, and proliferation, driven by sorafenib-induced upregulation and METTL3-mediated m<sup>6</sup>A methylation. Targeting the sorafenib-METTL3-m<sup>6</sup>A-PODN synergy offers a promising new therapeutic avenue for PTC.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"m<sup>6</sup>A Methylation of PODN Regulated by METTL3 Synergizes with Sorafenib to Exhibit Antitumor Function in Papillary Thyroid Cancer.\",\"authors\":\"Yanlei Sun, Bolu Sun, Mei Yang, Qiangqun Deng\",\"doi\":\"10.1007/s10528-025-11201-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Podocan (PODN) has strong clinical diagnostic significance, and sorafenib is a versatile anti-cancer drug. Yet, neither the individual nor combined effects of PODN and sorafenib on papillary thyroid carcinoma (PTC) malignancy, nor their mechanisms, have been reported. We employed bioinformatics to pinpoint mRNAs significantly downregulated in PTC that negatively affected tumor cell migration. Using qRT-PCR, we quantified PODN and Methyltransferase-like 3 (METTL3) levels in PTC samples. MeRIP, Pearson analysis, and RIP assays validated regulatory links among PODN, METTL3, and IGF2BP1. We treated PTC cells with sorafenib or induced PODN overexpression, then assessed proliferation, migration, and invasion via CCK-8, wound healing, and Transwell assays. Both PODN and METTL3 showed low expression in PTC samples and correlated positively. Sorafenib or high PODN levels suppressed PTC cell survival, migration, and invasion. Elevated PODN also amplified sorafenib's antitumor effects in PTC cells. Moreover, METTL3 increased N6-methyladenosine (m<sup>6</sup>A) methylation of PODN, upregulating PODN mRNA and protein via an IGF2BP1-dependent mechanism. Our findings indicate that PODN inhibits PTC cell invasion, migration, and proliferation, driven by sorafenib-induced upregulation and METTL3-mediated m<sup>6</sup>A methylation. Targeting the sorafenib-METTL3-m<sup>6</sup>A-PODN synergy offers a promising new therapeutic avenue for PTC.</p>\",\"PeriodicalId\":482,\"journal\":{\"name\":\"Biochemical Genetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-07-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemical Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s10528-025-11201-4\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10528-025-11201-4","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
m6A Methylation of PODN Regulated by METTL3 Synergizes with Sorafenib to Exhibit Antitumor Function in Papillary Thyroid Cancer.
Podocan (PODN) has strong clinical diagnostic significance, and sorafenib is a versatile anti-cancer drug. Yet, neither the individual nor combined effects of PODN and sorafenib on papillary thyroid carcinoma (PTC) malignancy, nor their mechanisms, have been reported. We employed bioinformatics to pinpoint mRNAs significantly downregulated in PTC that negatively affected tumor cell migration. Using qRT-PCR, we quantified PODN and Methyltransferase-like 3 (METTL3) levels in PTC samples. MeRIP, Pearson analysis, and RIP assays validated regulatory links among PODN, METTL3, and IGF2BP1. We treated PTC cells with sorafenib or induced PODN overexpression, then assessed proliferation, migration, and invasion via CCK-8, wound healing, and Transwell assays. Both PODN and METTL3 showed low expression in PTC samples and correlated positively. Sorafenib or high PODN levels suppressed PTC cell survival, migration, and invasion. Elevated PODN also amplified sorafenib's antitumor effects in PTC cells. Moreover, METTL3 increased N6-methyladenosine (m6A) methylation of PODN, upregulating PODN mRNA and protein via an IGF2BP1-dependent mechanism. Our findings indicate that PODN inhibits PTC cell invasion, migration, and proliferation, driven by sorafenib-induced upregulation and METTL3-mediated m6A methylation. Targeting the sorafenib-METTL3-m6A-PODN synergy offers a promising new therapeutic avenue for PTC.
期刊介绍：
Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses.
Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication.
Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses.
Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods.
Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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