Exploration of RNA-binding proteins identified RPS27 as a potential regulator associated with Kaposi's sarcoma development.

BACKGROUND

Kaposi's sarcoma (KS) is a locally aggressive, multicentric tumor. RNA-binding proteins (RBPs) are pivotal for post-transcriptional regulation in various tumors. However, the aberrantly expressed RBP genes and their regulatory patterns in KS remain unclear. This study aimed to identify relevant RBP genes in KS and assess the potential functions and molecular interactions of RPS27, a dysregulated RBP in KS tissues, METHODS: Matched KS lesions and normal control tissues from ten patients were chosen for the study. Differentially expressed genes (DEGs) were first identified by RNA-sequencing, and results were validated through an independent public RNA-seq dataset (GSE147704). Among the DEGs, RBPs were selected for further analysis, with RPS27 chosen for detailed investigation due to its dysregulation in KS tissues. RT-qPCR and immunohistochemistry were employed to validate RPS27 expression. Cellular experiments were conducted for dysregulated RPS27 to explore its functions. Additionally, improved RNA immunoprecipitation (iRIP)-seq was performed to investigate potential binding interactions of RPS27 in KS.

RESULTS

We identified 828 DEGs through RNA-seq, with 367 overlapping DEGs confirmed by the public RNA-seq dataset. We obtained 48 RBP genes from the overlapping DEGs, including 3 upregulated (PCBP3, L1TD1, and PEG10) and 45 downregulated RBP genes in KS. Notably, downregulated RBPs included TECR, PUSL1, DQX1, MAT1A, RACK1, EEF1A2, and EEF1B2, and the remaining downregulated RBPs were all ribosomal protein genes, including RPS27, which was selected for further exploration. Cellular experiments confirmed that RPS27 inhibition could promote cellular proliferation, migration, invasion, and angiogenesis of HUVECs, consistent with its downregulation in KS. iRIP-seq and RNA-seq analyses showed RPS27's ability to selectively bind to 26 DEGs and showed correlation. The majority of RPS27-bound DEGs were ribosomal protein genes, including RPL8, RPL13, RPL13A, RPL18, RPL19, RPL23, RPLP1, RPL27A, RPL40, RPS2, RPS4X, RPS13, RPS18, RPS21, and RPS27, which were associated with viral transcription and gene expression.

CONCLUSION

Our results identified dysregulated RBP genes in KS and explored the cellular functions and molecular targets of RPS27, indicating its potential regulatory role in KS development.