Baicalin induces ferroptosis in oral squamous cell carcinoma by suppressing the activity of FTH1

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2024-02-21 DOI:10.1002/jgm.3669

Zhihao Wen, Yuxiao Zhang, Bo Gao, Xin Chen

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Abstract

Background

This study investigated the role of the ferroptosis-related gene FTH1 in oral squamous cell carcinoma (OSCC) and evaluated the therapeutic potential of baicalin in OSCC cell treatment.

Methods

A prognostic model was established by bioinformatic analysis, consisting of 12 ferroptosis related genes (FRGs), and FTH1 was selected as the most significantly up-regulated FRGs. The clinical correlation of FTH1 in OSCC samples was evaluated by both immunohistochemical and bioinformatic characterizations. The effects of FTH1 on migration, invasion, epithelial–mesenchymal transition (EMT) and proliferation were determined by wound healing assays, transwell assays, western blotting and 5′-ethynl 2′-deoxyuridine proliferation assays, respectively. The effects of FTH1 on ferroptosis were tested via ferroptosis markers and Mito Tracker staining. In addition, the therapeutic effects of baicalin on OSCC cells were confirmed using EMT, migration, invasion, proliferation and ferroptosis assays.

Results

The 12 FRGs were predictive of the prognosis for OSCC patients, and FTH1 expression was identified as significantly up-regulated in OSCC samples, which was highly associated with survival, immune cell infiltration and drug sensitivity. Moreover, knocking down FTH1 inhibited cell proliferation, EMT and invasive phenotypes, but induced ferroptosis in OSCC cells (Cal27 and SCC25). Furthermore, baicalin directly suppressed expression of FTH1 in OSCC cells, and effectively promoted ferroptosis and inhibited the proliferation as well as EMT by directly targeting FTH1.

Conclusions

This study has demonstrated that FTH1 is a therapeutic target for OSCC treatment, and has provided evidence that baicalin offers a promising alternative for OSCC treatment.

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黄芩苷通过抑制 FTH1 的活性诱导口腔鳞状细胞癌的铁变态反应

背景：本研究探讨了铁突变相关基因FTH1在口腔鳞状细胞癌（OSCC）中的作用，并评估了黄芩苷治疗OSCC细胞的潜力：方法：通过生物信息学分析建立了由12个铁突变相关基因（FRGs）组成的预后模型，其中FTH1被认为是上调最显著的铁突变相关基因。通过免疫组化和生物信息分析评估了FTH1在OSCC样本中的临床相关性。FTH1对迁移、侵袭、上皮-间质转化（EMT）和增殖的影响分别通过伤口愈合试验、Transwell试验、Western印迹和5'-乙炔-2'-脱氧尿苷增殖试验进行了测定。FTH1 对铁凋亡的影响通过铁凋亡标记物和 Mito Tracker 染色进行检测。此外，黄芩苷对 OSCC 细胞的治疗作用还通过 EMT、迁移、侵袭、增殖和铁突变试验得到了证实：结果：12种FRGs可预测OSCC患者的预后，其中FTH1的表达在OSCC样本中显著上调，与存活率、免疫细胞浸润和药物敏感性高度相关。此外，在 OSCC 细胞（Cal27 和 SCC25）中，敲除 FTH1 可抑制细胞增殖、EMT 和侵袭表型，但会诱导铁变态反应。此外，黄芩苷直接抑制了FTH1在OSCC细胞中的表达，并通过直接靶向FTH1有效地促进了铁凋亡，抑制了细胞的增殖和EMT：本研究证明了FTH1是OSCC的治疗靶点，并为黄芩苷治疗OSCC提供了一种有前景的选择。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.