<br>ACKR1的高表达可预测良好的预后并通过调节肿瘤免疫微环境抑制肉瘤细胞的进展,Journal of Applied Genetics

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ACKR1的高表达可预测良好的预后并通过调节肿瘤免疫微环境抑制肉瘤细胞的进展
Journal of Applied Genetics ( IF 2.0 ) Pub Date : 2023-11-25 , DOI: 10.1007/s13353-023-00805-4
Jinluan Lin _{1,

2,

3,

4} , Fude Liang _{1,

2,

3,

4} , Lifeng Zheng _{1,

2,

3,

4} , Jinyuan Zeng _{1,

2,

3,

4} , Jianhua Lin _{1,

2,

3,

4}

Affiliation

肉瘤是一种起源于间叶组织的恶性肿瘤，预后较差。研究发现非典型趋化因子受体 1 (ACKR1) 与癌症进展密切相关。然而，ACKR1 在软组织肉瘤中的作用尚未得到充分研究。因此，我们目前的研究致力于分析ACKR1在肉瘤进展中的功能及其潜在机制。我们在癌症基因组图谱（TCGA）-泛癌数据库中检测到ACKR1的表达，在TCGA数据库中检测到TCGA-肉瘤，在基因表达综合（GEO）数据库中检测到GSE21122。在 TCGA-肉瘤数据库中评估了 ACKR1 表达、临床病理数据和生存状态之间的关系。此外，使用过表达阴性对照（OE-NC）和过表达ACKR1（OE-ACKR1）通过逆转录定量聚合酶链反应（RT-qPCR）进一步验证ACKR1过表达对肉瘤细胞进展的影响，细胞计数试剂盒 8 (CCK-8)、5-Ethyny-2'-脱氧尿苷 (EdU)、伤口愈合、Transwell 测定和流式细胞术测定。进行基因本体论（GO）、京都基因和基因组百科全书（KEGG）和基因集富集分析（GSEA）分析，以探索肉瘤中ACKR1表达的潜在富集生物学过程。此外，应用肿瘤免疫系统相互作用数据库（TISIDB）进一步证实肉瘤中ACKR1与肿瘤免疫微环境之间的关系。我们的研究发现ACKR1在多种癌症（包括肉瘤）中表达下调，并且ACKR1的低表达与肉瘤中较差的生存状态有关。生物学实验发现，促进ACKR1的表达可以抑制肉瘤细胞的增殖、迁移、侵袭，促进细胞凋亡，阻滞细胞周期。 GO-KEGG、GSEA、TISIDB分析表明ACKR1与肿瘤免疫微环境相关。总之，ACKR1 的低表达是肉瘤中独立的预后生物标志物。 ACKR1的过表达可以通过调节免疫微环境来显着抑制肉瘤中的细胞进展能力。

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High expression of ACKR1 predicts a good prognosis and suppresses sarcoma cell progression via regulating the tumor immune microenvironment

Sarcoma is a malignant tumor originating from mesenchymal tissue with a poor prognosis. Atypical chemokine receptor 1 (ACKR1) is found closely related to cancer progression. However, the effects of ACKR1 in soft tissue sarcoma have not been well investigated. Therefore, our present study is devoted to analyze the functions of ACKR1 in sarcoma progression and its potential mechanism. We detected the expression of ACKR1 in the Cancer Genome Atlas (TCGA)-pan-cancer database, TCGA-Sarcoma from TCGA databases, and GSE21122 from Gene Expression Omnibus (GEO) database. The relationships between ACKR1 expression, clinicopathological data, and survival status were evaluated in the TCGA-Sarcoma database. Moreover, overexpression negative control (OE-NC) and overexpression ACKR1 (OE-ACKR1) were used to further verify the effects of ACKR1 overexpression in the progression of sarcoma cells by using Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR), cell counting kit-8 (CCK-8), 5-Ethyny-2’-Deoxyuridine (EdU), wound healing, transwell assay, and flow cytometry assays. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analyses were carried out to explore the potential enriched biological process of ACKR1 expression in sarcoma. Furthermore, tumor-immune system interactions databases (TISIDB) were applied to further confirm the relations between ACKR1 and tumor immune microenvironment in sarcoma. Our study found that ACKR1 is downregulated in multiple cancers (including sarcoma), and low expression of ACKR1 is related to poor survival status in sarcoma. The biological experiments found that promoting expression of ACKR1 can suppress sarcoma cell proliferation, migration, invasion, promote cell apoptosis, and arrest cell cycle. The GO-KEGG, GSEA, and TISIDB analysis showed that ACKR1 is related to the tumor immune microenvironment. In conclusion, low expression of ACKR1 presented as an independent prognostic biomarker in sarcoma. Overexpression of ACKR1 can significantly suppress cell progression ability in sarcoma by regulating the immune microenvironment.

更新日期：2023-11-28

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