Yunnan Baiyao exerts anti-glioma activity by inducing autophagy-dependent necroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Yunnan Baiyao (YB), a traditional herbal formulation, has been used for over a century to manage bleeding and enhance blood circulation. Its ingredients are widely recognized for their anti-cancer properties. However, its impact on glioma, the most common primary malignant tumor of the central nervous system, remains unexplored. AIM OF THE STUDY: This study aims to investigate the anti-glioma activity of YB in vitro and in vivo, and to elucidate the underlying mechanism of action. METHODS: U-87 MG cells were treated with YB and subjected to cell proliferation assay, colony formation assay, and flow cytometry with Annexin V/PI staining to confirm anti-glioma activity. The induction of necroptosis and autophagy was confirmed through live-cell imaging, western blotting, and immunofluorescence analysis. The role of apoptosis, necroptosis, autophagy, and AMPK was validated using specific inhibitors. The in vivo anti-glioma activity of YB was evaluated using subcutaneous and orthotopic xenograft models in nude mice and chemically induced glioma rat models. RESULTS: YB induced necroptotic rather than apoptotic cell death in glioma U-87 MG cells, as evidenced by increased phosphorylated MLKL levels and plasma membrane disruptions. Rescue experiments further confirmed the role of necroptosis. Importantly, YB-triggered necroptosis was found to be dependent on autophagy induction, which relies on the AMPK signaling pathway. In line with these findings, YB demonstrated significant anti-glioma activity in vivo. CONCLUSIONS: Our study reveals that YB exerts potent anti-glioma effects both in vitro and in vivo through the induction of autophagy-dependent necroptosis.

Construction of a competing endogenous RNA network in head and neck squamous cell carcinoma by pan-cancer analysis.

Background: Head and neck squamous cell carcinoma (HNSC) is the sixth most common cancer worldwide, and new cases are anticipated to reach 1.08 million in 2030. Our study aimed to identify the competing endogenous RNAs (ceRNAs) involved in HNSC tumorigenesis. Methods: First, a pan-cancer correlation analysis was conducted on the expression and survival conditions of sideroflexin (SFXN3) based on data downloaded from the Xena database. Second, the upstream regulatory microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) of SFXN3 were predicted using the Encyclopedia of RNA Interactomes (ENCORI) database. Expression and survival analyses were subsequently used to construct lncRNA-miRNA-mRNA ceRNA network that correlated with HNSC. Third, the proportion of various types of immune cells in HNSC was calculated using the CIBERSORT algorithm. Finally, a correlation analysis was performed on SFXN3, including immune cell infiltration (ICI), clinical stage, and immune checkpoints. Results: The pan-cancer analysis suggested that SFXN3 was up-regulated in HNSC, and it correlated with poor prognosis. The ceRNA regulatory network MIR193BHG-miR-29c-3p-SFXN3 was identified as one of the potential biological regulatory pathways of HNSC. The upstream lncRNA MIR193BHG was associated with a poor prognosis in HNSC, and its target gene SFXN3 was correlated with tumor ICI, immune cell biomarkers, and immune checkpoints. Conclusions: By performing ceRNA analysis, our study demonstrated that MIR193HG-miR-29c-3p-SFXN3 is significantly involved in HNSC, and this action axis markedly affect the therapeutic effect and prognosis.