Maryam Latarani, Perla Pucci, Mark Eccleston, Massimiliano Manzo, Priyadarsini Gangadharannambiar, Ilaria Alborelli, Vera Mongiardini, Namra Mahmood, Mario Paolo Colombo, Benedetto Grimaldi, Sushila Rigas, Shusuke Akamatsu, Cheryl Hawkes, Yuzhuo Wang, Elena Jachetti, Francesco Crea
{"title":"抑制 EHZ2 可增强侵袭性变异前列腺癌的铂类化疗活性","authors":"Maryam Latarani, Perla Pucci, Mark Eccleston, Massimiliano Manzo, Priyadarsini Gangadharannambiar, Ilaria Alborelli, Vera Mongiardini, Namra Mahmood, Mario Paolo Colombo, Benedetto Grimaldi, Sushila Rigas, Shusuke Akamatsu, Cheryl Hawkes, Yuzhuo Wang, Elena Jachetti, Francesco Crea","doi":"10.1101/2024.09.06.611612","DOIUrl":null,"url":null,"abstract":"Background. EZH2 promotes aggressive-variant prostate cancer (AVPC) progression via histone H3-Lysine-27 tri-methylation (H3K27me3). We hypothesize that epigenetic reprogramming via EZH2 inhibitors (EZH2i) improves the efficacy of chemotherapy in AVPC.\nMethods. We studied the expression of EZH2 in clinical prostate cancer cohorts (bioinformatics). We determined the effect of EZH2i on both cellular and cell free-H3K27me3 levels. We measured effects of carboplatin with/without EZH2i on AVPC cell viability (IC50). We studied how EZH2i modulate gene expression (RNA Seq).\nResults. EZH2 was significantly up-regulated in AVPC vs other prostate cancer types. EZH2i reduced both cellular and cell free-H3K27me3 levels. EZH2i significantly reduced carboplatin IC50. EZH2i reduced the expression of DNA repair and increased the expression of pro-apoptotic genes.","PeriodicalId":501518,"journal":{"name":"bioRxiv - Pharmacology and Toxicology","volume":"17 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"EHZ2 inhibition enhances the activity of platinum chemotherapy in aggressive variant prostate cancer\",\"authors\":\"Maryam Latarani, Perla Pucci, Mark Eccleston, Massimiliano Manzo, Priyadarsini Gangadharannambiar, Ilaria Alborelli, Vera Mongiardini, Namra Mahmood, Mario Paolo Colombo, Benedetto Grimaldi, Sushila Rigas, Shusuke Akamatsu, Cheryl Hawkes, Yuzhuo Wang, Elena Jachetti, Francesco Crea\",\"doi\":\"10.1101/2024.09.06.611612\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background. EZH2 promotes aggressive-variant prostate cancer (AVPC) progression via histone H3-Lysine-27 tri-methylation (H3K27me3). We hypothesize that epigenetic reprogramming via EZH2 inhibitors (EZH2i) improves the efficacy of chemotherapy in AVPC.\\nMethods. We studied the expression of EZH2 in clinical prostate cancer cohorts (bioinformatics). We determined the effect of EZH2i on both cellular and cell free-H3K27me3 levels. We measured effects of carboplatin with/without EZH2i on AVPC cell viability (IC50). We studied how EZH2i modulate gene expression (RNA Seq).\\nResults. EZH2 was significantly up-regulated in AVPC vs other prostate cancer types. EZH2i reduced both cellular and cell free-H3K27me3 levels. EZH2i significantly reduced carboplatin IC50. EZH2i reduced the expression of DNA repair and increased the expression of pro-apoptotic genes.\",\"PeriodicalId\":501518,\"journal\":{\"name\":\"bioRxiv - Pharmacology and Toxicology\",\"volume\":\"17 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"bioRxiv - Pharmacology and Toxicology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.09.06.611612\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv - Pharmacology and Toxicology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.09.06.611612","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
EHZ2 inhibition enhances the activity of platinum chemotherapy in aggressive variant prostate cancer
Background. EZH2 promotes aggressive-variant prostate cancer (AVPC) progression via histone H3-Lysine-27 tri-methylation (H3K27me3). We hypothesize that epigenetic reprogramming via EZH2 inhibitors (EZH2i) improves the efficacy of chemotherapy in AVPC.
Methods. We studied the expression of EZH2 in clinical prostate cancer cohorts (bioinformatics). We determined the effect of EZH2i on both cellular and cell free-H3K27me3 levels. We measured effects of carboplatin with/without EZH2i on AVPC cell viability (IC50). We studied how EZH2i modulate gene expression (RNA Seq).
Results. EZH2 was significantly up-regulated in AVPC vs other prostate cancer types. EZH2i reduced both cellular and cell free-H3K27me3 levels. EZH2i significantly reduced carboplatin IC50. EZH2i reduced the expression of DNA repair and increased the expression of pro-apoptotic genes.
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