SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon Adenocarcinoma

Background: Ferroptosis induced by SLC7A11 has an important translational value in the treatment of cancers. However, the mechanism of SLC7A11 in the pathogenesis of colon adenocarcinoma (COAD) is rarely studied in detail.Methods: SLC7A11 expression was explored with The Cancer Genome Atlas (TCGA),...

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Main Authors: Xin Cheng, Yadong Wang, Liangchao Liu, Chenggang Lv, Can Liu, Jingyun Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2022.889688/full
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author Xin Cheng
Yadong Wang
Liangchao Liu
Chenggang Lv
Can Liu
Jingyun Xu
author_facet Xin Cheng
Yadong Wang
Liangchao Liu
Chenggang Lv
Can Liu
Jingyun Xu
author_sort Xin Cheng
collection DOAJ
description Background: Ferroptosis induced by SLC7A11 has an important translational value in the treatment of cancers. However, the mechanism of SLC7A11 in the pathogenesis of colon adenocarcinoma (COAD) is rarely studied in detail.Methods: SLC7A11 expression was explored with The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, and Western blot assay. The correlation of SLC7A11 expression with the abundance of infiltrating immune cells was evaluated via the TIMER database. The relation of SLC7A11 expression with immune cell markers was investigated via Gene Expression Profiling Interactive Analysis (GEPIA). The co-expression genes of SLC7A11 were screened by R packages, and the PPI was constructed via the STRING database. SLC7A11 and co-expressed gene modulators were selected by NetworkAnalyst and DSigDB database. The correlations between SLC7A11 and cancer immune characteristics were analyzed via the TIMER and TISIDB databases.Results: SLC7A11 is overexpressed in most tumors, including COAD. The expression level of SLC7A11 has a significant correlation with the infiltration levels of CD8+ T cells, neutrophils, and dendritic cells in COAD. The infiltrated lymphocyte markers of Th1 cell such as TBX21, IL12RB2, IL27RA, STAT1, and IFN-γ were strongly correlated with SLC7A11 expression. Five hub genes co-expressed with SLC7A11 that induce ferroptosis were identified, and mir-335-5p, RELA, and securinine have regulatory effects on it. SLC7A11 was negatively correlated with the expression of chemokines and chemokine receptors, such as CCL17, CCL19, CCL22, CCL23, CXCL14, CCR10, CX3CR1, and CXCR3, in COAD.Conclusion: SLC7A11 may play a role in induced ferroptosis and regulating tumor immunity, which can be considered as potential therapeutic targets in COAD.
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spelling doaj.art-be3f205e64f84e009a75be11dd2088142022-12-22T02:01:43ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-04-01910.3389/fmolb.2022.889688889688SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon AdenocarcinomaXin Cheng0Yadong Wang1Liangchao Liu2Chenggang Lv3Can Liu4Jingyun Xu5General Surgery Department, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, ChinaGeneral Surgery Department, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, ChinaGeneral Surgery Department, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, ChinaGeneral Surgery Department, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, ChinaThe First Affiliated Hospital of Wannan Medical College, Wuhu, ChinaSchool of Basic Medicine, Wannan Medical College, Wuhu, ChinaBackground: Ferroptosis induced by SLC7A11 has an important translational value in the treatment of cancers. However, the mechanism of SLC7A11 in the pathogenesis of colon adenocarcinoma (COAD) is rarely studied in detail.Methods: SLC7A11 expression was explored with The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, and Western blot assay. The correlation of SLC7A11 expression with the abundance of infiltrating immune cells was evaluated via the TIMER database. The relation of SLC7A11 expression with immune cell markers was investigated via Gene Expression Profiling Interactive Analysis (GEPIA). The co-expression genes of SLC7A11 were screened by R packages, and the PPI was constructed via the STRING database. SLC7A11 and co-expressed gene modulators were selected by NetworkAnalyst and DSigDB database. The correlations between SLC7A11 and cancer immune characteristics were analyzed via the TIMER and TISIDB databases.Results: SLC7A11 is overexpressed in most tumors, including COAD. The expression level of SLC7A11 has a significant correlation with the infiltration levels of CD8+ T cells, neutrophils, and dendritic cells in COAD. The infiltrated lymphocyte markers of Th1 cell such as TBX21, IL12RB2, IL27RA, STAT1, and IFN-γ were strongly correlated with SLC7A11 expression. Five hub genes co-expressed with SLC7A11 that induce ferroptosis were identified, and mir-335-5p, RELA, and securinine have regulatory effects on it. SLC7A11 was negatively correlated with the expression of chemokines and chemokine receptors, such as CCL17, CCL19, CCL22, CCL23, CXCL14, CCR10, CX3CR1, and CXCR3, in COAD.Conclusion: SLC7A11 may play a role in induced ferroptosis and regulating tumor immunity, which can be considered as potential therapeutic targets in COAD.https://www.frontiersin.org/articles/10.3389/fmolb.2022.889688/fullSLC7A11ferroptosisimmune infiltrateimmune microenvironmentCOAD
spellingShingle Xin Cheng
Yadong Wang
Liangchao Liu
Chenggang Lv
Can Liu
Jingyun Xu
SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon Adenocarcinoma
Frontiers in Molecular Biosciences
SLC7A11
ferroptosis
immune infiltrate
immune microenvironment
COAD
title SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon Adenocarcinoma
title_full SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon Adenocarcinoma
title_fullStr SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon Adenocarcinoma
title_full_unstemmed SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon Adenocarcinoma
title_short SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon Adenocarcinoma
title_sort slc7a11 a potential therapeutic target through induced ferroptosis in colon adenocarcinoma
topic SLC7A11
ferroptosis
immune infiltrate
immune microenvironment
COAD
url https://www.frontiersin.org/articles/10.3389/fmolb.2022.889688/full
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AT chengganglv slc7a11apotentialtherapeutictargetthroughinducedferroptosisincolonadenocarcinoma
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