Tanshinone IIA targets RNF123 to inhibit non-small cell lung cancer cell proliferation, migration and invasion via KAT2B-mediated H3K18ac modification.

Tanshinone IIA (TSIIA) exerts antitumor effects. The present study aimed to explore the pharmacological effect of TSIIA on lung cancer development and assess the potential underlying mechanism of action. Cell viability and proliferation were assessed using Cell Counting Kit-8 and 5-ethynyl-20-deoxyuridine assays, respectively. Transwell assays were performed to determine cell migration and invasion. Histone H3 lysine 18 acetylation (H3K18ac) and histone H4 lysine 8 acetylation (H4K8ac) enrichment in the RING finger protein 123 (RNF123) promoter and the interaction between lysine acetyltransferase 2B (KAT2B) and the RNF123 promoter were analyzed by chromatin immunoprecipitation assays. The results indicated that RNF123 was weakly expressed in lung cancer cells, and its upregulation decreased lung cancer cell viability, proliferation, migration, invasion and epithelial-mesenchymal transition. Sodium TSIIA sulfate (STS) treatment inhibited the non-small cell lung cancer (NSCLC) cell malignant phenotypes, which were reversed by the knockdown of RNF123. Mechanistically, TSIIA promoted KAT2B-mediated H3K18ac modification at the promoter region of the RNF123 gene, leading to upregulated RNF123 expression in NSCLC cells. Additionally, KAT2B knockdown prevented the STS-induced inhibition of NSCLC cell malignant phenotypes. Furthermore, RNF123 upregulation restored the effect of KAT2B knockdown on STS-treated NSCLC phenotypes. In conclusion, TSIIA inhibited the NSCLC cell malignant phenotypes via the epigenetic modification of RNF123.