Research on the Mechanism of Lphn1 Knockout in Inhibiting Colorectal Cancer

bioRxiv Pub Date : 2024-08-09 DOI:10.1101/2024.08.07.606975
Yi Wang
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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.
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Lphn1 基因敲除抑制结直肠癌的机制研究
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。
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