LINC00887 regulates malignant progression and T-cell chemotaxis in clear cell renal cell carcinoma by activating CD70 via recruitment of SPI1

Abstract

BackgroundLINC00887 has been mentioned in several articles regarding its involvement in various cancers like nasopharyngeal carcinoma, lung cancer and glioma. However, the mechanism of LINC00887 in the malignant progression of clear cell renal cell carcinoma (ccRCC) is still unclear. The topic of our study is mainly centered on exploring how LINC00887 exactly affects ccRCC malignant progression. MethodsThe bioinformatics method predicted the downstream TF and target genes of LINC00887 by the “LncRNA-transcription factor (TF)-Gene” triplet model. RNA immunoprecipitation, chromatin immunoprecipitation analysis, and Dual-luciferase reporter assay determined the regulatory relationship between LINC00887 and its downstream genes. The LINC00887 expression and its downstream gene expression in ccRCC cells were examined by qRT-PCR and Western blot. The effect of LINC00887-SPI1-CD70 modulation axis on proliferative transfer, cell stemness and T cell chemotaxis of ccRCC cells was examined in cellular and animal experiments. ResultsOur research demonstrated an upregulation of LINC00887 in ccRCC, which facilitated tumor growth and stemness in vivo. In addition, LINC00887 could upregulate the CD70 expression by recruiting transcriptional factor SPI1. The results of in vitro experiments illustrated that the LINC00887-SPI1-CD70 regulatory axis facilitated ccRCC malignant progression by promoting cell stemness and hindering T-cell chemotaxis. ConclusionLINC00887, by recruiting SPI1, activated CD70 transcription, thereby propelling malignant progression and cell stemness and suppressing T cell chemotaxis in ccRCC. Based on our findings, we believed that the LINC00887-SPI1-CD70 regulatory axis had the potential to be a critical breakthrough for treating ccRCC.