鉴定 SLC7A11-AS1/SLC7A11 对作为肝细胞癌铁死亡相关治疗靶点。
Identification of SLC7A11-AS1/SLC7A11 pair as a ferroptosis-related therapeutic target for hepatocellular carcinoma.
发表日期:2024 Jul
作者:
Xiao Yuan, Yida Wang, Sitong Jiao, Huanhuan Gao, Mengqian Zhang, Xin Wang, Xunyu Zhou, Chuanfang Wu, Jinku Bao
来源:
Cell Death & Disease
摘要:
肝细胞癌(HCC)是世界范围内普遍存在的恶性肿瘤,在预后方面提出了重大挑战,需要创新的治疗方法。铁死亡比细胞凋亡具有显着的优势,有望成为治疗复杂性 HCC 的新型治疗方法。此外,虽然长链非编码RNA(lncRNA)和mRNA之间的相互作用在各种生理和病理过程中至关重要,但它们在铁死亡中的作用仍然相对未被探索。在本研究中,我们利用 Pearson 相关分析构建了 HCC 中铁死亡相关的 lncRNA-mRNA 相关网络。值得注意的是,鉴定出具有高度相关性的 SLC7A11-AS1/SLC7A11 对。生物信息学分析显示,该对的表达水平与 HCC 患者的关键临床特征(包括性别、病理、Ishak 评分和肿瘤大小)之间存在显着相关性。不良预后与这对基因的高表达有关。功能实验表明,SLC7A11-AS1通过与SLC7A11 mRNA的3'UTR区域结合,增强其稳定性,从而促进HCC细胞生长并抵抗erastin诱导的铁死亡。此外,体内研究证实 SLC7A11-AS1 敲除增强了erastin对肿瘤生长的抑制作用。总体而言,我们的研究结果表明,针对 SLC7A11-AS1/SLC7A11 对有望成为 HCC 患者的潜在治疗策略。© 2024 作者。细胞与分子医学基金会和约翰·威利出版的《细胞与分子医学杂志》
Hepatocellular carcinoma (HCC), a prevalent malignancy worldwide, poses significant challenges in terms of prognosis, necessitating innovative therapeutic approaches. Ferroptosis offers notable advantages over apoptosis, holding promise as a novel therapeutic approach for HCC complexities. Moreover, while the interaction between long non-coding RNAs (lncRNAs) and mRNAs is pivotal in various physiological and pathological processes, their involvement in ferroptosis remains relatively unexplored. In this study, we constructed a ferroptosis-related lncRNA-mRNA correlation network in HCC using Pearson correlation analysis. Notably, the SLC7A11-AS1/SLC7A11 pair, exhibiting high correlation, was identified. Bioinformatics analysis revealed a significant correlation between the expression levels of this pair and key clinical characteristics of HCC patients, including gender, pathology, Ishak scores and tumour size. And poor prognosis was associated with high expression of this pair. Functional experiments demonstrated that SLC7A11-AS1, by binding to the 3'UTR region of SLC7A11 mRNA, enhanced its stability, thereby promoting HCC cell growth and resistance to erastin- induced ferroptosis. Additionally, in vivo studies confirmed that SLC7A11-AS1 knockdown potentiated the inhibitory effects of erastin on tumour growth. Overall, our findings suggest that targeting the SLC7A11-AS1/SLC7A11 pair holds promise as a potential therapeutic strategy for HCC patients.© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.