Establishment and Validation of a Ferroptosis-Related Long Non-Coding RNA Signature for Predicting the Prognosis of Stomach Adenocarcinoma.
Establishment and Validation of a Ferroptosis-Related Long Non-Coding RNA Signature for Predicting the Prognosis of Stomach Adenocarcinoma.
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DOI：
10.3389/fgene.2022.818306
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发表时间：
2022
影响因子：
3.7
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Zhang S;Zheng N;Chen X;Du K;Yang J;Shen L
背景：铁凋亡是细胞膜损伤后的一种调节性细胞死亡形式，主要依赖于铁介导的氧化。长链非编码RNA（LncRNA）与多种肿瘤的发生有关。迄今为止，已报道LncRNA干预铁凋亡。因此，我们打算提供胃腺癌（STAD）中的预后铁中毒相关lncRNA标记。 研究方法：我们从FerDb数据库中下载了铁中毒相关基因，并从癌症基因组图谱中下载了RNA测序数据和临床病理特征。使用“limma”软件包进行基因差异表达分析。我们使用考克斯回归分析来确定具有最低AIC值的铁中毒相关lncRNA特征。采用Kaplan-Meier曲线、ROC曲线和列线图评价风险评分的预后价值。采用基因集富集分析（Gene set enrichment analysis，GSEA）方法研究三种铁中毒相关lncRNA的生物学功能。采用实时荧光定量PCR检测胃癌细胞株和组织中LINC 01615的表达。使用核质分级分离测定来分析LINC 01615的亚细胞定位。此外，我们使用生物信息学来预测LINC 01615的潜在靶microRNAs（miRNAs）及其靶向铁蛋白分解相关mRNA。 结果如下：经Kaplan-Meier、考克斯回归分析和ROC曲线分析，证实了铁凋亡相关lncRNA模型可以预测STAD的预后。GSEA结果表明，三种铁中毒相关lncRNA可能与细胞外基质和细胞活动有关。LINC 01615在胃癌细胞系和组织中高度表达。核质分级分析证实，在胃癌细胞系中，大多数LINC 01615富集在细胞质中。生物信息学进一步预测了LINC 01615的4个潜在靶miRNAs，并最终确定了26个与铁凋亡相关的靶miRNAs。 结论：我们建立了三个铁凋亡相关lncRNA模型（AP000695.2，AL365181.3和LINC 01615），可以预测STAD患者的预后。LINC 01615在胃癌和胃癌细胞株中高表达，可作为ceRNA参与铁凋亡的研究，为今后的研究提供了一个有前景的靶点。
Background: Ferroptosis is a form of regulated cell death that follows cell membrane damage and mostly depends on iron-mediated oxidative. Long non-coding RNAs (LncRNAs) are associated with the development of a variety of tumors. Till date, LncRNAs have been reported to intervene in ferroptosis. Therefore, we intended to provide a prognostic ferroptosis-related-lncRNA signature in stomach adenocarcinoma (STAD). Methods: We downloaded ferroptosis-related genes from the FerrDb database and RNA sequencing data and clinicopathological characteristics from The Cancer Genome Atlas. Gene differential expression analysis was performed using the “limma” package. We used Cox regression analysis to determine the ferroptosis-related lncRNAs signature with the lowest AIC value. The Kaplan–Meier curve, ROC curve, and nomogram were used to evaluate the prognostic value of the risk score. Gene set enrichment analysis (GSEA) was used to explore the biologic functions of the three ferroptosis-related lncRNAs. LINC01615 expression in gastric cancer cell lines and tissues was measured by real-time PCR. A nuclear-cytoplasmic fractionation assay was used to analyze the subcellular localization for LINC01615. Furthermore, we used bioinformatics to predict potential target microRNAs (miRNAs) of LINC01615 and their target ferroptosis-related mRNAs. Results: Three ferroptosis-related-lncRNA signatures (AP000695.2, AL365181.3, and LINC01615) were identified, and then Kaplan–Meier, Cox regression analyses, and ROC curve confirmed that the ferroptosis-related-lncRNA model could predict the prognosis of STAD. The GSEA indicated that the three ferroptosis-related lncRNAs might be related to the extracellular matrix and cellular activities. LINC01615 is highly expressed in gastric cancer cell lines and tissues. A nuclear-cytoplasmic fractionation assay confirmed that in gastric cancer cell lines, most LINC01615 was enriched in the cytoplasm. Bioinformatics further predicts four potential target miRNAs of LINC01615 and then figured out 26 target ferroptosis-related mRNAs. Conclusion: We established a three-ferroptosis-related-lncRNA model (AP000695.2, AL365181.3, and LINC01615) that can predict the prognosis of STAD patients. We also expected to provide a promising target for LINC01615 for research in the future, which was highly expressed in gastric cancer and cell lines and acted as a ceRNA to get involved in ferroptosis.
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DOI：
10.1111/jop.13267
发表时间：
2022-01
期刊：
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
影响因子：
--
作者：
Lu T;Zhang Z;Pan X;Zhang J;Wang X;Wang M;Li H;Yan M;Chen W
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Chen W
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Xing L
影响因子：
3.1
作者：
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Tan, Pingqing
影响因子：
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Lu, Jingjing;Xu, Feng;Lu, Hong
通讯作者：
Lu, Hong
影响因子：
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作者：
Shi, Ying;Huang, Xiaoxiao;Ren, Jianlin
通讯作者：
Ren, Jianlin