{"title":"Lphn1 基因敲除抑制结直肠癌的机制研究","authors":"Yi Wang","doi":"10.1101/2024.08.07.606975","DOIUrl":null,"url":null,"abstract":"Decades ago, colorectal cancer was rarely diagnosed. Today, it is the fourth leading cause of cancer-related deaths worldwide, with nearly 90,000 fatalities each year. By analyzing single-cell data from tumor-bearing colorectal cancer model mice with Lphn1 knockout and wild-type Lphn1, we identified five key target genes for anticancer therapy: Ulbp1, Klrk1, Ccl6, Tlr4, Cd48, Prdm5, VSTM2A, RET, OAS2, Hdac11 and Ptchd4, along with their corresponding cell types. Additionally, we discovered tumor-inhibiting cell subpopulations, including Cd244a_T_cells_subcluster_1, Cd48_Cd244a_NK_cells_subcluster_2, and C3_Macrophages_subcluster_1, which are potential candidates for therapeutic intervention. We propose that cancer-associated fibroblasts (CAFs) serve as the primary antigen presenters for MHC class I, providing antigens to macrophages, NK cells, and T cells to combat colorectal cancer. These findings could open new avenues for the treatment of colorectal cancer and contribute to the development of personalized medicine.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Research on the Mechanism of Lphn1 Knockout in Inhibiting Colorectal Cancer\",\"authors\":\"Yi Wang\",\"doi\":\"10.1101/2024.08.07.606975\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Decades ago, colorectal cancer was rarely diagnosed. Today, it is the fourth leading cause of cancer-related deaths worldwide, with nearly 90,000 fatalities each year. By analyzing single-cell data from tumor-bearing colorectal cancer model mice with Lphn1 knockout and wild-type Lphn1, we identified five key target genes for anticancer therapy: Ulbp1, Klrk1, Ccl6, Tlr4, Cd48, Prdm5, VSTM2A, RET, OAS2, Hdac11 and Ptchd4, along with their corresponding cell types. Additionally, we discovered tumor-inhibiting cell subpopulations, including Cd244a_T_cells_subcluster_1, Cd48_Cd244a_NK_cells_subcluster_2, and C3_Macrophages_subcluster_1, which are potential candidates for therapeutic intervention. We propose that cancer-associated fibroblasts (CAFs) serve as the primary antigen presenters for MHC class I, providing antigens to macrophages, NK cells, and T cells to combat colorectal cancer. These findings could open new avenues for the treatment of colorectal cancer and contribute to the development of personalized medicine.\",\"PeriodicalId\":505198,\"journal\":{\"name\":\"bioRxiv\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"bioRxiv\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.08.07.606975\",\"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","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.08.07.606975","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
几十年前,人们很少诊断出结直肠癌。如今,它已成为全球癌症相关死亡的第四大原因,每年有近 90,000 人死于此病。通过分析Lphn1基因敲除和野生型Lphn1的肿瘤结直肠癌模型小鼠的单细胞数据,我们发现了抗癌治疗的五个关键靶基因:Ulbp1、Klrk1、Ccl6、Tlr4、Cd48、Prdm5、VSTM2A、RET、OAS2、Hdac11 和 Ptchd4,以及它们相应的细胞类型。此外,我们还发现了抑制肿瘤的细胞亚群,包括Cd244a_T_cells_subcluster_1、Cd48_Cd244a_NK_cells_subcluster_2和C3_Macrophages_subcluster_1,它们是治疗干预的潜在候选细胞。我们提出,癌症相关成纤维细胞(CAFs)是 MHC I 类的主要抗原呈递者,为巨噬细胞、NK 细胞和 T 细胞提供抗原,以对抗结直肠癌。这些发现将为治疗结直肠癌开辟新的途径,并促进个性化医疗的发展。
Research on the Mechanism of Lphn1 Knockout in Inhibiting Colorectal Cancer
Decades ago, colorectal cancer was rarely diagnosed. Today, it is the fourth leading cause of cancer-related deaths worldwide, with nearly 90,000 fatalities each year. By analyzing single-cell data from tumor-bearing colorectal cancer model mice with Lphn1 knockout and wild-type Lphn1, we identified five key target genes for anticancer therapy: Ulbp1, Klrk1, Ccl6, Tlr4, Cd48, Prdm5, VSTM2A, RET, OAS2, Hdac11 and Ptchd4, along with their corresponding cell types. Additionally, we discovered tumor-inhibiting cell subpopulations, including Cd244a_T_cells_subcluster_1, Cd48_Cd244a_NK_cells_subcluster_2, and C3_Macrophages_subcluster_1, which are potential candidates for therapeutic intervention. We propose that cancer-associated fibroblasts (CAFs) serve as the primary antigen presenters for MHC class I, providing antigens to macrophages, NK cells, and T cells to combat colorectal cancer. These findings could open new avenues for the treatment of colorectal cancer and contribute to the development of personalized medicine.