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SLC7A1 Overexpression Is Involved in Energy Metabolism Reprogramming to Induce Tumor Progression in Epithelial Ovarian Cancer and Is Associated with Immune-Infiltrating Cells

Cationic amino acid transporters (SLC7A1/CAT1) are highly expressed in human ovarian cancer (OC) tissues. However, the specific biological functions and mechanisms involved remain unclear. We used bioinformatics analysis to explore SLC7A1 expression level, prognostic value, and tumor mutation burden...

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Autores principales: You, Shijing, Zhu, Xiaoying, Yang, Yao, Du, XiuZhen, Song, Kejuan, Zheng, Qingmei, Zeng, Pengjiao, Yao, Qin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484923/
https://www.ncbi.nlm.nih.gov/pubmed/36131790
http://dx.doi.org/10.1155/2022/5864826
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author You, Shijing
Zhu, Xiaoying
Yang, Yao
Du, XiuZhen
Song, Kejuan
Zheng, Qingmei
Zeng, Pengjiao
Yao, Qin
author_facet You, Shijing
Zhu, Xiaoying
Yang, Yao
Du, XiuZhen
Song, Kejuan
Zheng, Qingmei
Zeng, Pengjiao
Yao, Qin
author_sort You, Shijing
collection PubMed
description Cationic amino acid transporters (SLC7A1/CAT1) are highly expressed in human ovarian cancer (OC) tissues. However, the specific biological functions and mechanisms involved remain unclear. We used bioinformatics analysis to explore SLC7A1 expression level, prognostic value, and tumor mutation burden (TMB) in ovarian cancer (OC) tissues. We performed in vitro experiments to identify the expression and biological function of SLC7A1 in epithelial ovarian cancer (EOC) tissues and cells. An amino acid autoanalyzer was used to detect the effect of SLC7A1 on amino acid metabolism in EOC cells. Finally, SLC7A1 in OC was evaluated for cell-to-cell signalling and immune infiltration using online databases. We found that increased SLC7A1 expression in EOC cells and tissues was associated with poorer survival outcomes (P < 0.05) but not with tumor stage or grade of OC (P > 0.05). SLC7A1 is involved in the transport of phenylalanine and arginine in EOC cells, and its knockdown reduced the proliferation and migration of EOC cells and the resistance of cells to cisplatin. Furthermore, the TIMER database indicated that SLC7A1 overexpression was significantly positively correlated with levels of CD4(+) memory resting cells, CD8(+) effector memory cells, M0 macrophages, and cancer-associated fibroblasts (CAFs) in OC (P < 0.05) and significantly negatively correlated with CD4(+) memory-activated cells (P < 0.05). Cell immunofluorescence indicated that SLC7A1 overexpression may affect the distribution of immune-infiltrating lymphocytes in tumors by inhibiting the expression of CCL4. Therefore, we concluded that SLC7A1 is involved in the metabolic remodelling of amino acids in EOC to promote tumor development and cisplatin resistance and is related to the tumor-infiltrating immune microenvironment of OC. SLC7A1 is a biomarker for predicting EOC progression and cisplatin resistance and represents a promising target for EOC treatment.
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spelling pubmed-94849232022-09-20 SLC7A1 Overexpression Is Involved in Energy Metabolism Reprogramming to Induce Tumor Progression in Epithelial Ovarian Cancer and Is Associated with Immune-Infiltrating Cells You, Shijing Zhu, Xiaoying Yang, Yao Du, XiuZhen Song, Kejuan Zheng, Qingmei Zeng, Pengjiao Yao, Qin J Oncol Research Article Cationic amino acid transporters (SLC7A1/CAT1) are highly expressed in human ovarian cancer (OC) tissues. However, the specific biological functions and mechanisms involved remain unclear. We used bioinformatics analysis to explore SLC7A1 expression level, prognostic value, and tumor mutation burden (TMB) in ovarian cancer (OC) tissues. We performed in vitro experiments to identify the expression and biological function of SLC7A1 in epithelial ovarian cancer (EOC) tissues and cells. An amino acid autoanalyzer was used to detect the effect of SLC7A1 on amino acid metabolism in EOC cells. Finally, SLC7A1 in OC was evaluated for cell-to-cell signalling and immune infiltration using online databases. We found that increased SLC7A1 expression in EOC cells and tissues was associated with poorer survival outcomes (P < 0.05) but not with tumor stage or grade of OC (P > 0.05). SLC7A1 is involved in the transport of phenylalanine and arginine in EOC cells, and its knockdown reduced the proliferation and migration of EOC cells and the resistance of cells to cisplatin. Furthermore, the TIMER database indicated that SLC7A1 overexpression was significantly positively correlated with levels of CD4(+) memory resting cells, CD8(+) effector memory cells, M0 macrophages, and cancer-associated fibroblasts (CAFs) in OC (P < 0.05) and significantly negatively correlated with CD4(+) memory-activated cells (P < 0.05). Cell immunofluorescence indicated that SLC7A1 overexpression may affect the distribution of immune-infiltrating lymphocytes in tumors by inhibiting the expression of CCL4. Therefore, we concluded that SLC7A1 is involved in the metabolic remodelling of amino acids in EOC to promote tumor development and cisplatin resistance and is related to the tumor-infiltrating immune microenvironment of OC. SLC7A1 is a biomarker for predicting EOC progression and cisplatin resistance and represents a promising target for EOC treatment. Hindawi 2022-09-12 /pmc/articles/PMC9484923/ /pubmed/36131790 http://dx.doi.org/10.1155/2022/5864826 Text en Copyright © 2022 Shijing You et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
You, Shijing
Zhu, Xiaoying
Yang, Yao
Du, XiuZhen
Song, Kejuan
Zheng, Qingmei
Zeng, Pengjiao
Yao, Qin
SLC7A1 Overexpression Is Involved in Energy Metabolism Reprogramming to Induce Tumor Progression in Epithelial Ovarian Cancer and Is Associated with Immune-Infiltrating Cells
title SLC7A1 Overexpression Is Involved in Energy Metabolism Reprogramming to Induce Tumor Progression in Epithelial Ovarian Cancer and Is Associated with Immune-Infiltrating Cells
title_full SLC7A1 Overexpression Is Involved in Energy Metabolism Reprogramming to Induce Tumor Progression in Epithelial Ovarian Cancer and Is Associated with Immune-Infiltrating Cells
title_fullStr SLC7A1 Overexpression Is Involved in Energy Metabolism Reprogramming to Induce Tumor Progression in Epithelial Ovarian Cancer and Is Associated with Immune-Infiltrating Cells
title_full_unstemmed SLC7A1 Overexpression Is Involved in Energy Metabolism Reprogramming to Induce Tumor Progression in Epithelial Ovarian Cancer and Is Associated with Immune-Infiltrating Cells
title_short SLC7A1 Overexpression Is Involved in Energy Metabolism Reprogramming to Induce Tumor Progression in Epithelial Ovarian Cancer and Is Associated with Immune-Infiltrating Cells
title_sort slc7a1 overexpression is involved in energy metabolism reprogramming to induce tumor progression in epithelial ovarian cancer and is associated with immune-infiltrating cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484923/
https://www.ncbi.nlm.nih.gov/pubmed/36131790
http://dx.doi.org/10.1155/2022/5864826
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