Identification of a key ceRNA network associated with ferroptosis in gastric cancer.

Identification of a key ceRNA network associated with ferroptosis in gastric cancer.
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鉴定与胃癌螺旋菌病有关的关键CERNA网络。

DOI:
10.1038/s41598-022-24402-3
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发表时间:
2022-11-22
期刊:
影响因子:
4.6
通讯作者:
Yu, Lan
Yu, Lan
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jin, Wen;Liu, Jianli;Yang, Jie;Feng, Zongqi;Feng, Zhenxing;Huang, Na;Yang, Tingyu;Yu, Lan

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铁凋亡是一种新发现的由脂质过氧化物过度积累引起的受调控细胞死亡的铁依赖性形式,与包括胃癌(GC)在内的各种类型癌症的发展和治疗反应有关。非编码rna (ncRNAs)作为癌症的关键调控因子,具有致癌和抑瘤双重作用。然而,GC中与嗜铁性凋亡相关的ncRNA网络的研究仍然缺乏。在这里,我们首先通过计算和分析胃癌肿瘤和正常组织的基因表达谱,确定了61个与胃癌铁下垂相关的差异表达基因。然后通过miRNet和miRBase数据库找到上游lncrna和与其相互作用的mirna,通过拓扑分析获得枢纽lncrna和mirna。最后,建立了GC中与铁下垂相关的ceRNA调控网络,包括两个铁下垂标记基因(TXNIP和TSC22D3)、一个驱动基因(GABARAPL1)和一个抑制基因(CAV1)。Kaplan-Meier生存分析显示,这些基因表达的变化与胃癌患者的生存有关。此外,我们的研究表明,该ceRNA网络可能通过调节铁下垂过程影响GC的进展。这些结果将有助于实验研究人员设计实验研究,进一步探索该调控网络在GC铁下垂中的作用。
Ferroptosis, a newly discovered irondependent form of regulated cell death caused by excessive accumulation of lipid peroxides, is linked to the development and treatment response of various types of cancer, including gastric cancer (GC). Noncoding RNAs (ncRNAs), as key regulators in cancer, have both oncogenic and tumor suppressive roles. However, studies on ferroptosis-related ncRNA networks in GC are still lacking. Here, we first identified 61 differentially expressed genes associated with ferroptosis in GC by computing and analyzing gene expression profile of tumor and normal tissues for GC. Then, upstream lncRNAs and miRNAs interacting with them were found through miRNet and miRBase databases, and hub lncRNAs and miRNAs were obtained through topological analysis. Finally, the ceRNA regulatory network linked to ferroptosis in GC was established, which includes two ferroptosis marker genes (TXNIP and TSC22D3), one driver gene (GABARAPL1), and one suppressor gene (CAV1). Kaplan-Meier survival analysis showed that changes in the expression of these genes were associated with the survival of GC patients. Furthermore, our study revealed that this ceRNA network may influence the progression of GC by regulating ferroptosis process. These results will help experimental researchers to design an experiment study to further explore the roles of this regulatory network in GC ferroptosis.
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