IL6ST: A Novel Therapeutic Target for Managing and Treating Colorectal Cancer Via Ferroptosis.

IF 1.4 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Turkish Journal of Gastroenterology Pub Date : 2024-06-06 DOI:10.5152/tjg.2024.23353
Kun Zhao, Baoguo He, Kuijin Xue, Bin Cao, Keyu Ren, Yanchun Jin, Shanwei Rong, Liangzhou Wei, Hongyun Wei
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Abstract

Inflammation is an essential driver of colorectal cancer (CRC). Identifying phenotypes and targets associated with inflammation and cancer may be an effective way to treat CRC. R was used to analyze interleukin 6 cytokine family signal transducer (IL6ST) expression in The Cancer Genome Atlas Colon Adenocarcinoma database. Immunohistochemistry, western blotting, and quantitative PCR were used to detect IL6ST and ferroptosis-related genes expression in our cohort. Receiver operating characteristic curves evaluated the specificity and sensitivity of IL6ST to predict CRC. Cell counting kit-8 investigated cell viability. Mitochondrial morphology, total iron, and reactive oxygen species (ROS) levels were evaluated to assess cell ferroptosis. The correlation of IL6ST and immune cells filtration were also analyzed based on R. IL6ST was significantly upregulated in CRC tissues (P < .05). The specificity and sensitivity of IL6ST for predicting CRC were high (area under the curve (AUC): 0.919, CI: 0.896-0.942). IL6ST was significantly associated with ferroptosis-related genes. IL6ST knockdown decreased SW480 cells viability (knockdown vs. vector, P = .004), promoted the ferroptosis phenotype, and increased iron accumulation (knockdown vs. vector P = .014) and ROS production (knockdown vs. vector P = .005). IL6ST upregulation increased SW620 cells viability (overexpression vs. blank, P = .001), inhibited the ferroptosis phenotype, and decreased iron accumulation (overexpression vs. vector P = 0.006) and ROS production (overexpression vs. vector P = .05). IL6ST increased FTH1 and GPX4 expression and reduced PTGS2, NOX1, and ACSL4 expression (P < .01). Additionally, IL6ST level is linked to immune cell infiltration. A higher enrichment score of T cells was observed in IL6ST up-regulated group. IL6ST inhibits ferroptosis and may be a potential novel therapeutic target in CRC via the modulation of ferroptosis.

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IL6ST:通过铁凋亡管理和治疗结直肠癌的新治疗靶点。
炎症是结直肠癌(CRC)的重要诱因。确定与炎症和癌症相关的表型和靶点可能是治疗 CRC 的有效方法。研究人员使用 R 来分析癌症基因组图谱结肠腺癌数据库中白细胞介素 6 细胞因子家族信号转导因子(IL6ST)的表达。免疫组化、Western 印迹和定量 PCR 被用于检测队列中 IL6ST 和铁蛋白沉积相关基因的表达。接收者操作特征曲线评估了IL6ST预测CRC的特异性和敏感性。细胞计数试剂盒-8检测细胞活力。评估线粒体形态、总铁和活性氧(ROS)水平是为了评估细胞铁变态反应。IL6ST 在 CRC 组织中显著上调(P < .05)。IL6ST 预测 CRC 的特异性和灵敏度都很高(曲线下面积 (AUC):0.919,CI:0.896-0.942)。IL6ST 与铁突变相关基因明显相关。IL6ST 敲除会降低 SW480 细胞的存活率(敲除与载体相比,P = .004),促进铁突变表型,增加铁积累(敲除与载体相比,P = .014)和 ROS 生成(敲除与载体相比,P = .005)。IL6ST 的上调提高了 SW620 细胞的存活率(过表达 vs. 空白,P = .001),抑制了铁变态表型,减少了铁积累(过表达 vs. 载体,P = 0.006)和 ROS 生成(过表达 vs. 载体,P = .05)。IL6ST 增加了 FTH1 和 GPX4 的表达,减少了 PTGS2、NOX1 和 ACSL4 的表达(P < .01)。此外,IL6ST 水平还与免疫细胞浸润有关。在 IL6ST 上调组观察到更高的 T 细胞富集分数。IL6ST可抑制铁凋亡,可能是通过调节铁凋亡治疗 CRC 的潜在新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Turkish Journal of Gastroenterology
Turkish Journal of Gastroenterology 医学-胃肠肝病学
CiteScore
1.90
自引率
0.00%
发文量
127
审稿时长
6 months
期刊介绍: The Turkish Journal of Gastroenterology (Turk J Gastroenterol) is the double-blind peer-reviewed, open access, international publication organ of the Turkish Society of Gastroenterology. The journal is a bimonthly publication, published on January, March, May, July, September, November and its publication language is English. The Turkish Journal of Gastroenterology aims to publish international at the highest clinical and scientific level on original issues of gastroenterology and hepatology. The journal publishes original papers, review articles, case reports and letters to the editor on clinical and experimental gastroenterology and hepatology.
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