研究动态
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SMC1A对结肠腺癌免疫微环境和癌症干细胞的影响。

Effects of SMC1A on immune microenvironment and cancer stem cells in colon adenocarcinoma.

发表日期:2023 Apr 25
作者: Jin Li, Qian Zhou, Li Liu, Jingdong He
来源: GENES & DEVELOPMENT

摘要:

我们之前的研究表明SMC1在结直肠癌(CRC)中有重要的功能。然而,很少有报道显示染色体结构维护1(SMC1A)对免疫微环境和肿瘤干细胞的影响。使用癌症基因组图谱(TCGA)数据库、临床蛋白质组分析计划(CPTAC)数据库、人类蛋白质图谱数据库(HPA)、癌细胞系百科全书(CCLE)和肿瘤免疫单细胞中心。通过流式细胞术和免疫组化分析检查MC38小鼠模型的免疫浸润。采用RT-qPCR检测人CRC组织。在结直肠腺癌(COAD)样本中,SMC1A的mRNA和蛋白水平增加。SMC1A与DNA活性有关。有趣的是,在单个细胞水平上,SMC1A在许多类型的免疫细胞中高表达。此外,高表达的SMC1A与免疫浸润呈正相关,免疫组化分析显示,在MC38小鼠模型中,SMC1A与CD45表达呈正相关。此外,流式细胞术检测显示,与对照组相比,SMC1A过表达组中IL4+ CD4+ T细胞(Th2)和FoxP3+ CD4+ T细胞(Tregs)的百分比显著更高。SMC1A表达可影响小鼠模型中T细胞的增殖。SMC1A的突变和体细胞拷贝数变异(SCNV)也与免疫细胞浸润有关。除了结肠癌的“热点”T细胞炎症微环境中的SMC1A外,SMC1A还与结直肠腺癌(COAD)样本中的免疫检查点基因CD274、CTLA4和PDCD1呈正相关。此外,我们还发现SMC1A与诱导癌干细胞(CSCs)的正相关。我们的结果还表明,miR-23b-3p与SMC1A结合。SMC1A可能是一个双向的目标开关,同时调节免疫微环境和肿瘤干细胞。此外,SMC1A也可能是预测免疫检查点抑制剂(IC1)治疗的生物标志物。©2023年该文章作者。由约翰威立出版社出版的癌症医学杂志。
Our previous study suggested that SMC1 has significant functions in colorectal cancer (CRC). However, few reports have shown the effects of structural maintenance of chromosomes 1 (SMC1A) on the immune microenvironment and tumor stem cells.The Cancer Genome Atlas (TCGA) database, CPTAC database, Human Protein Atlas (HPA) database, the Cancer Cell Line Encyclopedia (CCLE) and Tumor Immune Single-cell Hub were used. Flow cytometry and immunohistochemical analysis were checked for immune infiltration on MC38 mice model. Human CRC tissues were tested with RT-qPCR.The mRNA and protein levels of SMC1A were increased in colon adenocarcinoma (COAD) samples. SMC1A was associated with DNA activity. Interestingly, SMC1A was highly expressed in many types of immune cells at single-cell levels. Moreover, the high expression of SMC1A was positively correlated with immune infiltration, and immunohistochemical analysis showed that SMC1A was positively associated with CD45 expression in MC38 mice model. Also, the percentage of IL4+ CD4+ T cells (Th2) and FoxP3+ CD4+ T cells (Tregs) was significantly higher in the SMC1A overexpression group than in control by flow cytometry assay in vivo. SMC1A expression could affect the proliferation of T cells in the mice model. The mutation and somatic cell copy number variation (SCNV) of SMC1A were also associated with immune cell infiltration. In addition to SMC1A in the "hot" T-cell inflammatory microenvironment of colon cancer, SMC1A also positively correlates with the immune checkpoint genes CD274, CTLA4, and PDCD1 in colon adenocarcinoma (COAD) samples. Furthermore, we also found that SMC1A plays a positive correlation with the induction of cancer stem cells (CSCs). Our results also showed that miR-23b-3p binds SMC1A.SMC1A may be a bidirectional target switch that simultaneously regulates the immune microenvironment and tumor stem cells. Moreover, SMC1A may be a biomarker for the prediction of immune checkpoint inhibitor (ICI) therapy.© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.