{"title":"靶向非人类物种特异性 lncRNA 的 siRNA 触发人类结直肠癌细胞死亡","authors":"Wan-Ying Feng, Jun-Xiang Zeng, Yan-Ru Chen, Zhe-Ping Fang, Yi Gao, Wei-Jie Zhou","doi":"10.7150/jca.99462","DOIUrl":null,"url":null,"abstract":"<p><p>Species-specific long non-coding RNAs (lncRNAs) possess numerous unknown functions. We have recently reported that short interfering RNAs (siRNAs) designed to target mouse-specific lncRNAs caused cell death exclusively in human cancer cells, sparing normal human cells and mouse cancer cells. However, it is uncertain whether other non-human species-specific lncRNAs could also be applied as sequential targets for designing anti-tumor therapeutic siRNAs. In this research, we showed that siRNAs targeting rat or zebrafish-specific lncRNAs could exert similar cytotoxic effects against human colorectal cancer (CRC) cells while leaving normal human cells unaffected. Mechanistic investigations revealed that these siRNAs prompted apoptosis or pyroptosis in human CRC cells by triggering an IRF3-independent immune response against exogenous dsRNAs, based on the expression of protein gasdermin E (GSDME). Our study demonstrates that utilizing siRNAs to target non-human species-specific lncRNAs can trigger cell death in human CRC cells, indicating that non-human species-specific lncRNAs could serve as a promising reservoir for target libraries when designing anti-tumor siRNAs.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"15 18","pages":"5956-5967"},"PeriodicalIF":3.3000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493012/pdf/","citationCount":"0","resultStr":"{\"title\":\"siRNAs Targeting Non-Human Species-Specific lncRNAs Trigger Cell Death in Human Colorectal Cancer Cells.\",\"authors\":\"Wan-Ying Feng, Jun-Xiang Zeng, Yan-Ru Chen, Zhe-Ping Fang, Yi Gao, Wei-Jie Zhou\",\"doi\":\"10.7150/jca.99462\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Species-specific long non-coding RNAs (lncRNAs) possess numerous unknown functions. We have recently reported that short interfering RNAs (siRNAs) designed to target mouse-specific lncRNAs caused cell death exclusively in human cancer cells, sparing normal human cells and mouse cancer cells. However, it is uncertain whether other non-human species-specific lncRNAs could also be applied as sequential targets for designing anti-tumor therapeutic siRNAs. In this research, we showed that siRNAs targeting rat or zebrafish-specific lncRNAs could exert similar cytotoxic effects against human colorectal cancer (CRC) cells while leaving normal human cells unaffected. Mechanistic investigations revealed that these siRNAs prompted apoptosis or pyroptosis in human CRC cells by triggering an IRF3-independent immune response against exogenous dsRNAs, based on the expression of protein gasdermin E (GSDME). Our study demonstrates that utilizing siRNAs to target non-human species-specific lncRNAs can trigger cell death in human CRC cells, indicating that non-human species-specific lncRNAs could serve as a promising reservoir for target libraries when designing anti-tumor siRNAs.</p>\",\"PeriodicalId\":15183,\"journal\":{\"name\":\"Journal of Cancer\",\"volume\":\"15 18\",\"pages\":\"5956-5967\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493012/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7150/jca.99462\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/jca.99462","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
siRNAs Targeting Non-Human Species-Specific lncRNAs Trigger Cell Death in Human Colorectal Cancer Cells.
Species-specific long non-coding RNAs (lncRNAs) possess numerous unknown functions. We have recently reported that short interfering RNAs (siRNAs) designed to target mouse-specific lncRNAs caused cell death exclusively in human cancer cells, sparing normal human cells and mouse cancer cells. However, it is uncertain whether other non-human species-specific lncRNAs could also be applied as sequential targets for designing anti-tumor therapeutic siRNAs. In this research, we showed that siRNAs targeting rat or zebrafish-specific lncRNAs could exert similar cytotoxic effects against human colorectal cancer (CRC) cells while leaving normal human cells unaffected. Mechanistic investigations revealed that these siRNAs prompted apoptosis or pyroptosis in human CRC cells by triggering an IRF3-independent immune response against exogenous dsRNAs, based on the expression of protein gasdermin E (GSDME). Our study demonstrates that utilizing siRNAs to target non-human species-specific lncRNAs can trigger cell death in human CRC cells, indicating that non-human species-specific lncRNAs could serve as a promising reservoir for target libraries when designing anti-tumor siRNAs.
期刊介绍:
Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.