Tanshinone IIA regulates microRNA‑125b/foxp3/caspase‑1 signaling and inhibits cell viability of nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a common disease with high prevalence worldwide, affecting hundreds of thousands of patients every year. Although its progress can be inhibited by concurrent chemoradiotherapy and platinum-based agents, there is also a need for novel drugs to treat NPC. The present study identified tanshinone IIA as a potent drug that could suppress the proliferation of HK1 cells by enhancing pyroptosis via regulation of the miR-125b/foxp3/caspase-1 signaling pathway. Firstly, the effects of tanshinone IIA on HK1 cells were assessed and it was confirmed that treatment with tanshinone IIA significantly decreased the proliferation of HK1 cells, with increased activity of caspase-3 and caspase-9. Then, the pyroptosis levels after tanshinone IIA administration were detected. The results showed that tanshinone IIA enhanced pyroptosis in a dose-dependent manner. Furthermore, the mechanism underlying the effects of tanshinone IIA on HK1 cells were explored. It was found that transfection with a microRNA (miR)-125b agomir and a small interfering RNA (si)-foxp3 plasmid reversed the inhibitory effect induced by tanshinone IIA, accompanied by an increase in reactive oxygen species levels and lactate dehydrogenase release, indicating a critical role of miR-125b/foxp3 signaling in pyroptosis in HK1 cells. In conclusion, the present study demonstrates that tanshinone IIA enhances pyroptosis and inhibits the proliferation of HK1 cells by modulating miR-125b/foxp3/caspase-1/GSDMD signaling. It is the first study to reveal the inhibitory effect of tanshinone IIA on HK1 cells and to demonstrate the critical role of miR-125b/foxp3 signaling in mediating these effects, providing robust evidence for the treatment of NPC.

Tanshinone IIA suppresses the progression of lung adenocarcinoma through regulating CCNA2-CDK2 complex and AURKA/PLK1 pathway

“…In recent years, research has shown that TSA has a cytotoxic effect on a series of tumor cells, Liu et al found that TSA alleviated colorectal tumorigenesis through inhibition of intestinal inflammation 12 . Wang et al found that TSA inhibited cell viability of nasopharyngeal carcinoma through regulating microRNA‑125b/foxp3/caspase‑1 signaling 13 . However, the role of TSA against LUAD remains unknown.…”

Noncoding RNAs in pyroptosis and cancer progression: Effect, mechanism, and clinical application

“…Additionally, miR-145/GSDMD signaling is regulated by tanshinone IIA, a lipophilic pharmacologically active compound extracted from Salvia miltiorrhiza Bunge (Danshen) ( 53 ). Similarly, tanshinone IIA enhances the pyroptosis in nasopharyngeal carcinoma (NPC) and suppresses the progression of NPC via miR−125b/foxp3/caspase−1/GSDMD signaling ( 54 ). Moreover, in enterovirus A71 (EV-A71)-infected human neuroblastoma, miR-195 inhibits pyroptosis by targeting NLRX1.…”

Salvia miltiorrhiza in cancer: Potential role in regulating MicroRNAs and epigenetic enzymes

“…Specific miRNAs directly or indirectly participate in the regulation of multiple apoptotic pathways by regulating the level of downstream genes, and they can play an oncogenic or tumor suppressor role ( Bejarano et al, 2021 ). Tan IIA targets miR-125b/gasdermin D (GSDMD) and miR-145/caspase 1, which induces apoptosis of nasopharyngeal carcinoma (NPC) cells (HK1 cells) and cervical carcinoma cells (HeLa cells), respectively ( Tong et al, 2020 ; Wang et al, 2021c ). In addition, tan IIA targets miR30b, further upregulating p53 levels, which induces apoptosis and death of HCC cells ( Ren et al, 2017 ).…”