Potential upstream lncRNA-miRNA-mRNA regulatory network of the ferroptosis-related gene SLC7A11 in renal cell carcinoma.

Abstract

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. 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. We confirmed that SLC7A11 was upregulated in most human cancers, including 3 types of RCC. SLC7A11 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). SLC7A11 expression was also linked to immune cell infiltration levels. After performing a comprehensive analysis of the regulatory mechanisms of SLC7A11 expression, the results depicted a potential noncoding (ncRNA)-messenger RNA (mRNA) axis, incorporating SNHG6-miR-26a-5p-SLC7A11 networks in KICH, CASC19/CYTOR/LINC00997-miR-27b-3pSLC7A11 networks in KIRC, and CASC19/CYTOR/PVT1-miR27b-3p-SLC7A11 networks in KIRP as partially responsible for the functions of SLC7A11 in RCC. SLC7A11 expression was positively linked to infiltrated immune cells and their matching marker sets in 3 types of RCC, including CD8+ and myeloid dendritic cells. 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.