ABSTRACT
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.
