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肾细胞癌中铁死亡相关基因的潜在上游长链非编码RNA-微小RNA-信使核糖核酸调控网络

Potential upstream lncRNA-miRNA-mRNA regulatory network of the ferroptosis-related gene in renal cell carcinoma.

作者信息

Xu Feng, Ji Shuya, Yang Lin, Li Yong, Shen Pei

机构信息

Department of Oncology, Shanghai Pudong New Area Gongli Hospital, Shanghai, China.

Department of Nephrology, Shanghai Pudong New Area Gongli Hospital, Shanghai, China.

出版信息

Transl Androl Urol. 2023 Jan 30;12(1):33-57. doi: 10.21037/tau-22-663. Epub 2023 Jan 11.

DOI:10.21037/tau-22-663
PMID:36760866
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9906110/
Abstract

BACKGROUND

SLC7A11 is a key regulator of ferroptosis, which mediates cysteine uptake for glutathione biosynthesis and maintains redox homeostasis. Emerging evidence has shown that SLC7A11 is upregulated in many human tumors. Nevertheless, the prognosis and posttranslational regulatory mechanism of SLC7A11 in renal cell carcinoma (RCC) remains obscure.

METHODS

The Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), and The Cancer Genome Atlas (TCGA) databases were used to analyze the difference in SLC7A11 expression between malignant and normal tissues. Furthermore, the GEPIA, the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), and starBase databases were used to conduct the survival analyses. For correlation analysis, the UALCAN and starBase databases were employed. The Tumor Immune Estimation Resource (TIMER) database was used to approximate the abundance of immune infiltration.

RESULTS

We confirmed that was upregulated in most human cancers, including 3 types of RCC. overexpression was linked to poor prognosis of individuals with kidney renal clear cell carcinoma (KIRC), kidney chromophobe cell carcinoma (KICH), and kidney renal papillary cell carcinoma (KIRP). expression was also linked to immune cell infiltration levels. After performing a comprehensive analysis of the regulatory mechanisms of expression, the results depicted a potential noncoding (ncRNA)-messenger RNA (mRNA) axis, incorporating -- networks in KICH, //- networks in KIRC, and //-- networks in KIRP as partially responsible for the functions of SLC7A11 in RCC. expression was positively linked to infiltrated immune cells and their matching marker sets in 3 types of RCC, including CD8 and myeloid dendritic cells.

CONCLUSIONS

Our research elucidated the crucial functions and the upstream long noncoding RNA (lncRNA)-microRNA (miRNA) regulatory network of SLC7A11 in RCC. Importantly, SLC7A11 can be used as a potential prognostic biomarker for 3 types of RCC and to determine the infiltration of immune cells in malignant tissues.

摘要

背景

溶质载体家族7成员11(SLC7A11)是铁死亡的关键调节因子,介导用于谷胱甘肽生物合成的半胱氨酸摄取并维持氧化还原稳态。新出现的证据表明,SLC7A11在许多人类肿瘤中上调。然而,SLC7A11在肾细胞癌(RCC)中的预后及翻译后调控机制仍不清楚。

方法

使用Oncomine、基因表达谱交互式分析(GEPIA)和癌症基因组图谱(TCGA)数据库分析恶性组织和正常组织中SLC7A11表达的差异。此外,使用GEPIA、阿拉巴马大学伯明翰分校癌症数据分析门户(UALCAN)和starBase数据库进行生存分析。进行相关性分析时,采用UALCAN和starBase数据库。肿瘤免疫估计资源(TIMER)数据库用于估算免疫浸润的丰度。

结果

我们证实SLC7A11在大多数人类癌症中上调,包括3种类型的RCC。SLC7A11过表达与肾透明细胞癌(KIRC)、肾嫌色细胞癌(KICH)和肾乳头状细胞癌(KIRP)患者的不良预后相关。SLC7A11表达也与免疫细胞浸润水平相关。在对SLC7A11表达的调控机制进行全面分析后,结果描绘了一个潜在的非编码(ncRNA)-信使核糖核酸(mRNA)轴,包括KICH中的lncRNA-miRNA-mRNA网络、KIRC中的lncRNA-miRNA网络以及KIRP中的lncRNA-miRNA-mRNA网络,这些网络部分负责SLC7A11在RCC中的功能。SLC7A11表达与3种类型RCC中浸润的免疫细胞及其匹配的标志物集呈正相关,包括CD8和髓样树突状细胞。

结论

我们的研究阐明了SLC7A11在RCC中的关键功能及其上游长链非编码核糖核酸(lncRNA)-微小核糖核酸(miRNA)调控网络。重要的是,SLC7A11可作为3种类型RCC的潜在预后生物标志物,并用于确定恶性组织中免疫细胞的浸润情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/aa172eb55be5/tau-12-01-33-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/114bae510280/tau-12-01-33-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/1ff3172926e8/tau-12-01-33-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/da544c6ac780/tau-12-01-33-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/87312088fd7a/tau-12-01-33-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/d893fd7b2a99/tau-12-01-33-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/58ac76d73a57/tau-12-01-33-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/b3e79edf38cc/tau-12-01-33-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/9ca7f601b3bc/tau-12-01-33-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/aa172eb55be5/tau-12-01-33-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/114bae510280/tau-12-01-33-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/1ff3172926e8/tau-12-01-33-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/da544c6ac780/tau-12-01-33-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/87312088fd7a/tau-12-01-33-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/d893fd7b2a99/tau-12-01-33-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/58ac76d73a57/tau-12-01-33-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/b3e79edf38cc/tau-12-01-33-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/9ca7f601b3bc/tau-12-01-33-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e78/9906110/aa172eb55be5/tau-12-01-33-f9.jpg

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