Abstract: To explore the effect of ribosomal protein RPS6 subunit peptide on S180 tumor cell gene expression and the key molecule and signal pathway of inhibiting tumor cells, using S180 tumor bearing mice as models, S180 tumor bearing mice were treated with RPS6 subunit peptide, and S180 tumor cells were sequenced by Illumina to obtain differentially expressed genes, and these differentially expressed genes were analyzed by GO and KEGG. Gene expression results showed that RPS6 subunit peptide could reduce the expression of mt-Cytb,mt-Nd1andRpl13genes, and hinder the oxidative phosphorylation process of S180 tumor cells. The results of GO analysis showed that the key categories of RPS6 subunit peptide inhibiting tumor cells focused on the changes of plasma membrane and its outer components, and the regulation of immune response and the activation of immune cells. The differential gene results showed that RPS6 subunit peptide could enhance PRL/PRLR signal, up regulateUchl1gene expression and induce tumor cell cycle arrest. The results of KEGG pathway enrichment showed that the expression of perforin encoded byPrf1and granzyme B encoded by Gzmb, together with cytotoxicity mediated by natural killer cells, participated in S180 tumor cell apoptosis under the effect of RPS6 subunit peptide. Meanwhile, TNF-α expression was up-regulated in NF-κB signal pathway, in coordination with up-regulated IFN-γin cell-mediated cytotoxicity pathway also jointly inhibiting the proliferation of S180 tumor cells. RPS6 subunit peptide led to cell cycle arrest of S180 tumor cells, induced cytotoxicity mediated by natural killer cells and up regulation of NF-κB signal pathway led to S180 tumor cell apoptosis, which provided a theoretical basis for the application of RPS6 subunit peptide in antitumor research.

Key words: ribosomal protein RPS6, small molecule peptides, RNA-Seq sequencing, differential expressed genes (DEGs), NF-κB pathway