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.

Background and aims: HOXD antisense growth-associated long noncoding RNA (HOXD-AS1) was reported to be upregulated in various cancers, such as gastric cancer, hepatocellular carcinoma, colorectal cancer, and glioma. Here, we conducted a meta-analysis and The Cancer Genome Atlas data review to investigate the clinicopathologic and prognostic value of HOXD-AS1 in patients with malignant tumors.Materials and methods: Systematic literatures were searched from PubMed, Medline, Cochrane Library, Web of Science, EMBASE database, Ovid, Chinese CNKI, and the Chinese WanFang database. The role of HOXD-AS1 in cancers was evaluated by pooled ORs and HRs with 95% CIs. The Cancer Genome Atlas dataset was used to explore the prognostic value of HOXD-AS1 in various cancers.ResultsFifteen studies with 1,678 patients were included in this meta-analysis. The results indicated that HOXD-AS1 was associated with tumor size, differentiation, lymph node metastasis, and TNM stage. Moreover, the high HOXD-AS1 expression indicated a poor overall survival (OS) rate and can be an independent predictive factor for OS. The TCGA dataset, which included 9,502 cancer patients, showed that the expression of HOXD-AS1 was related to poor OS and disease-free survival. We also analyzed the prognostic role in different kinds of cancers such as digestive cancers, female reproductive system cancers, respiratory system cancers, and urinary system cancers.ConclusionThis study demonstrated that HOXD-AS1 was closely correlated with tumor size, lymph node metastasis, distant metastasis, and TNM stage, and an increased HOXD-AS1 expression could be a reliable prognostic biomarker in human cancers. However, more studies are needed to confirm this conclusion.

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