Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1
Sphingolipid transporter 1 (SPNS1) is a significant differentially expressed gene (DEGs) in esophageal squamous cell carcinoma (ESCC). According to 3 pairs clinic cohorts, transcriptomic (155 pairs of ESCC samples and GSE53624, and proteomic data from PXD021701 including 124 ESCC samples) we found t...
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Elsevier
2024-04-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332224002518 |
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author | Xin Yang Ye Jiao Yingying Zhang Meng Sun Yingzhen Gao Yan Zhou Heng Xiao Jing Ren Zhinan Zhou Yuanfang Zhai Bin Song Ling Zhang Pengzhou Kong |
author_facet | Xin Yang Ye Jiao Yingying Zhang Meng Sun Yingzhen Gao Yan Zhou Heng Xiao Jing Ren Zhinan Zhou Yuanfang Zhai Bin Song Ling Zhang Pengzhou Kong |
author_sort | Xin Yang |
collection | DOAJ |
description | Sphingolipid transporter 1 (SPNS1) is a significant differentially expressed gene (DEGs) in esophageal squamous cell carcinoma (ESCC). According to 3 pairs clinic cohorts, transcriptomic (155 pairs of ESCC samples and GSE53624, and proteomic data from PXD021701 including 124 ESCC samples) we found that SPNS1 was significantly higher in ESCC tissues compared to adjacent normal esophagus tissues. ESCC patients with high SPNS1 had a significantly poorer clinical prognosis than those with low SPNS1. Knockdown of SPNS1 significantly inhibited the proliferation, migration, and invasion abilities of ESCC cells, while promoting apoptosis. And overexpression of SPNS1 exhibited opposite functions. Furthermore, ESCC cells became more sensitive to 5-fluorouracil (5-FU) when SPNS1 was knocked down. Transcriptome sequencing revealed that NEU1 was one significant DEG affected by SPNS1 and positively correlated with SPNS1 expression. Oseltamivir phosphate (OP), one NEU1 inhibitor, markedly reversed 5-FU resistance, migration, and proliferation induced by high expression of SPNS1 both in vivo and in vitro. Our findings indicated that SPNS1 might promote the progression of ESCC by upregulating NEU1 expression and influencing chemotherapy sensitivity. These results provide new perceptions into potential therapeutic targets for ESCC treatment. The present study aimed to investigate the role and underlying mechanism of SPNS1 in ESCC. |
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format | Article |
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language | English |
last_indexed | 2024-04-24T20:14:17Z |
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series | Biomedicine & Pharmacotherapy |
spelling | doaj.art-7aa6894c95c64528ac01bcab6ef536772024-03-23T06:22:53ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-04-01173116367Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1Xin Yang0Ye Jiao1Yingying Zhang2Meng Sun3Yingzhen Gao4Yan Zhou5Heng Xiao6Jing Ren7Zhinan Zhou8Yuanfang Zhai9Bin Song10Ling Zhang11Pengzhou Kong12Translational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaTranslational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Human Anatomy, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaCancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Shanxi, ChinaTranslational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, China; Correspondence to: Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaTranslational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Shanxi Medical University, Ministry of Education, China; Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, China; State Key Laboratory for Pneumoconiosis of National Health Commission, Key Laboratory of Prevention, Treatment and Fundamental Studies for Respiratory Diseases of Shanxi, Department of Respiratory and Critical Care Medicine, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China; Correspondence to: Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaSphingolipid transporter 1 (SPNS1) is a significant differentially expressed gene (DEGs) in esophageal squamous cell carcinoma (ESCC). According to 3 pairs clinic cohorts, transcriptomic (155 pairs of ESCC samples and GSE53624, and proteomic data from PXD021701 including 124 ESCC samples) we found that SPNS1 was significantly higher in ESCC tissues compared to adjacent normal esophagus tissues. ESCC patients with high SPNS1 had a significantly poorer clinical prognosis than those with low SPNS1. Knockdown of SPNS1 significantly inhibited the proliferation, migration, and invasion abilities of ESCC cells, while promoting apoptosis. And overexpression of SPNS1 exhibited opposite functions. Furthermore, ESCC cells became more sensitive to 5-fluorouracil (5-FU) when SPNS1 was knocked down. Transcriptome sequencing revealed that NEU1 was one significant DEG affected by SPNS1 and positively correlated with SPNS1 expression. Oseltamivir phosphate (OP), one NEU1 inhibitor, markedly reversed 5-FU resistance, migration, and proliferation induced by high expression of SPNS1 both in vivo and in vitro. Our findings indicated that SPNS1 might promote the progression of ESCC by upregulating NEU1 expression and influencing chemotherapy sensitivity. These results provide new perceptions into potential therapeutic targets for ESCC treatment. The present study aimed to investigate the role and underlying mechanism of SPNS1 in ESCC.http://www.sciencedirect.com/science/article/pii/S0753332224002518ESCCSPNS1Drug sensibilityNEU1Therapeutic targetsSurvival |
spellingShingle | Xin Yang Ye Jiao Yingying Zhang Meng Sun Yingzhen Gao Yan Zhou Heng Xiao Jing Ren Zhinan Zhou Yuanfang Zhai Bin Song Ling Zhang Pengzhou Kong Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1 Biomedicine & Pharmacotherapy ESCC SPNS1 Drug sensibility NEU1 Therapeutic targets Survival |
title | Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1 |
title_full | Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1 |
title_fullStr | Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1 |
title_full_unstemmed | Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1 |
title_short | Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1 |
title_sort | oseltamivir enhances 5 fu sensitivity in esophageal squamous carcinoma with high spns1 |
topic | ESCC SPNS1 Drug sensibility NEU1 Therapeutic targets Survival |
url | http://www.sciencedirect.com/science/article/pii/S0753332224002518 |
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