{"title":"LncRNA STEAP3-AS1通过染色质重塑调节组蛋白乳酸化，促进结直肠癌肝转移。","authors":"Jinjuan Lv, Xiaoqi Yu, Xiaoqian Liu, Qianshi Zhang, Mengyan Zhang, Jianfeng Gao, Zhiwei Sun, Feifan Zhang, Yunfei Zuo, Shuangyi Ren","doi":"10.1186/s13046-025-03461-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Liver metastasis is a common cause of death in patients with colorectal cancer (CRC); however, its molecular mechanism remains unclear. Here, we aimed to reveal the role of the lncRNA STEAP3-AS1 in regulating chromatin remodelling and histone lactylation and explore the mechanism by which the lncRNA STEAP3-AS1 promotes CRC liver metastasis. This study provide new research ideas and a theoretical basis for the clinical treatment of cancer.</p><p><strong>Methods: </strong>In this study, we used CRC organoid and nude mouse liver metastasis models to analyse the effect of the lncRNA STEAP3-AS1 on CRC liver metastasis. ATAC-seq, RNA-seq, DRIP-seq and Western blotting were used to screen for the lncRNA STEAP3-AS1 downstream prometastatic molecule MMP9 and the chromatin remodelling factor BRG1. The protein interactions between BRG1, p300, and HDAC3 were evaluated by Co-IP. The the binding of BRG1, ERG, P300, and H3K18la to the MMP9 gene promoter was detected using ChIP-qPCR.</p><p><strong>Results: </strong>The lncRNA STEAP3-AS1 interacts with its parental gene, STEAP3, to form an R-loop on the key chromatin remodelling factor BRG1, regulating the expression of BRG1. Further evidence suggests that BRG1 forms a protein complex with the histone lactylation eraser HDAC3 and the writer P300 to regulate the expression of H3K18la. Moreover, the ATAC-seq analysis revealed that the lncRNA STEAP3-AS1 promotes the chromatin accessibility of MMP9, and a motif and database analysis identified the tumour metastasis factor ERG as an MMP9 transcription factor. The lncRNA STEAP3-AS1 mediates regulation of H3K18la activation of MMP9 by the BRG1/ERG/P300 complex.</p><p><strong>Conclusions: </strong>In summary, these findings revealed that the lncRNA STEAP3-AS1 interacts with its parental gene STEAP3 to regulate H3K18la through BRG1, resulting in changes in chromatin accessibility, thereby driving ERG enrichment an the MMP9 promoter to activate MMP9 transcription and promote CRC liver metastasis. Our findings reveal a novel mechanism by which the lncRNA STEAP3-AS1 promotes CRC metastasis from an epigenetic perspective.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"205"},"PeriodicalIF":12.8000,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261760/pdf/","citationCount":"0","resultStr":"{\"title\":\"The LncRNA STEAP3-AS1 promotes liver metastasis in colorectal cancer by regulating histone lactylation through chromatin remodelling.\",\"authors\":\"Jinjuan Lv, Xiaoqi Yu, Xiaoqian Liu, Qianshi Zhang, Mengyan Zhang, Jianfeng Gao, Zhiwei Sun, Feifan Zhang, Yunfei Zuo, Shuangyi Ren\",\"doi\":\"10.1186/s13046-025-03461-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Liver metastasis is a common cause of death in patients with colorectal cancer (CRC); however, its molecular mechanism remains unclear. Here, we aimed to reveal the role of the lncRNA STEAP3-AS1 in regulating chromatin remodelling and histone lactylation and explore the mechanism by which the lncRNA STEAP3-AS1 promotes CRC liver metastasis. This study provide new research ideas and a theoretical basis for the clinical treatment of cancer.</p><p><strong>Methods: </strong>In this study, we used CRC organoid and nude mouse liver metastasis models to analyse the effect of the lncRNA STEAP3-AS1 on CRC liver metastasis. ATAC-seq, RNA-seq, DRIP-seq and Western blotting were used to screen for the lncRNA STEAP3-AS1 downstream prometastatic molecule MMP9 and the chromatin remodelling factor BRG1. The protein interactions between BRG1, p300, and HDAC3 were evaluated by Co-IP. The the binding of BRG1, ERG, P300, and H3K18la to the MMP9 gene promoter was detected using ChIP-qPCR.</p><p><strong>Results: </strong>The lncRNA STEAP3-AS1 interacts with its parental gene, STEAP3, to form an R-loop on the key chromatin remodelling factor BRG1, regulating the expression of BRG1. Further evidence suggests that BRG1 forms a protein complex with the histone lactylation eraser HDAC3 and the writer P300 to regulate the expression of H3K18la. Moreover, the ATAC-seq analysis revealed that the lncRNA STEAP3-AS1 promotes the chromatin accessibility of MMP9, and a motif and database analysis identified the tumour metastasis factor ERG as an MMP9 transcription factor. The lncRNA STEAP3-AS1 mediates regulation of H3K18la activation of MMP9 by the BRG1/ERG/P300 complex.</p><p><strong>Conclusions: </strong>In summary, these findings revealed that the lncRNA STEAP3-AS1 interacts with its parental gene STEAP3 to regulate H3K18la through BRG1, resulting in changes in chromatin accessibility, thereby driving ERG enrichment an the MMP9 promoter to activate MMP9 transcription and promote CRC liver metastasis. Our findings reveal a novel mechanism by which the lncRNA STEAP3-AS1 promotes CRC metastasis from an epigenetic perspective.</p>\",\"PeriodicalId\":50199,\"journal\":{\"name\":\"Journal of Experimental & Clinical Cancer Research\",\"volume\":\"44 1\",\"pages\":\"205\"},\"PeriodicalIF\":12.8000,\"publicationDate\":\"2025-07-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261760/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Experimental & Clinical Cancer Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13046-025-03461-0\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Experimental & Clinical Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13046-025-03461-0","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
The LncRNA STEAP3-AS1 promotes liver metastasis in colorectal cancer by regulating histone lactylation through chromatin remodelling.
Introduction: Liver metastasis is a common cause of death in patients with colorectal cancer (CRC); however, its molecular mechanism remains unclear. Here, we aimed to reveal the role of the lncRNA STEAP3-AS1 in regulating chromatin remodelling and histone lactylation and explore the mechanism by which the lncRNA STEAP3-AS1 promotes CRC liver metastasis. This study provide new research ideas and a theoretical basis for the clinical treatment of cancer.
Methods: In this study, we used CRC organoid and nude mouse liver metastasis models to analyse the effect of the lncRNA STEAP3-AS1 on CRC liver metastasis. ATAC-seq, RNA-seq, DRIP-seq and Western blotting were used to screen for the lncRNA STEAP3-AS1 downstream prometastatic molecule MMP9 and the chromatin remodelling factor BRG1. The protein interactions between BRG1, p300, and HDAC3 were evaluated by Co-IP. The the binding of BRG1, ERG, P300, and H3K18la to the MMP9 gene promoter was detected using ChIP-qPCR.
Results: The lncRNA STEAP3-AS1 interacts with its parental gene, STEAP3, to form an R-loop on the key chromatin remodelling factor BRG1, regulating the expression of BRG1. Further evidence suggests that BRG1 forms a protein complex with the histone lactylation eraser HDAC3 and the writer P300 to regulate the expression of H3K18la. Moreover, the ATAC-seq analysis revealed that the lncRNA STEAP3-AS1 promotes the chromatin accessibility of MMP9, and a motif and database analysis identified the tumour metastasis factor ERG as an MMP9 transcription factor. The lncRNA STEAP3-AS1 mediates regulation of H3K18la activation of MMP9 by the BRG1/ERG/P300 complex.
Conclusions: In summary, these findings revealed that the lncRNA STEAP3-AS1 interacts with its parental gene STEAP3 to regulate H3K18la through BRG1, resulting in changes in chromatin accessibility, thereby driving ERG enrichment an the MMP9 promoter to activate MMP9 transcription and promote CRC liver metastasis. Our findings reveal a novel mechanism by which the lncRNA STEAP3-AS1 promotes CRC metastasis from an epigenetic perspective.
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