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Construction of a paclitaxel-related competitive endogenous RNA network and identification of a potential regulatory axis in pancreatic cancer

BACKGROUND: Increasing numbers of studies have elucidated the role of competitive endogenous RNA (ceRNA) networks in carcinogenesis. However, the potential role of the paclitaxel-related ceRNA network in the innate mechanism and prognosis of pancreatic cancer has not been identified. METHODS: Compre...

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Autores principales: Lu, Si Yuan, Hua, Jie, Liu, Jiang, Wei, Miao Yan, Liang, Chen, Meng, Qing Cai, Zhang, Bo, Yu, Xian Jun, Wang, Wei, Xu, Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018166/
https://www.ncbi.nlm.nih.gov/pubmed/35413498
http://dx.doi.org/10.1016/j.tranon.2022.101419
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author Lu, Si Yuan
Hua, Jie
Liu, Jiang
Wei, Miao Yan
Liang, Chen
Meng, Qing Cai
Zhang, Bo
Yu, Xian Jun
Wang, Wei
Xu, Jin
author_facet Lu, Si Yuan
Hua, Jie
Liu, Jiang
Wei, Miao Yan
Liang, Chen
Meng, Qing Cai
Zhang, Bo
Yu, Xian Jun
Wang, Wei
Xu, Jin
author_sort Lu, Si Yuan
collection PubMed
description BACKGROUND: Increasing numbers of studies have elucidated the role of competitive endogenous RNA (ceRNA) networks in carcinogenesis. However, the potential role of the paclitaxel-related ceRNA network in the innate mechanism and prognosis of pancreatic cancer has not been identified. METHODS: Comprehensive bioinformatics analyses were performed to identify drug-related miRNAs (DRmiRNAs), drug-related mRNAs (DRmRNAs) and drug-related lncRNAs (DRlncRNAs) and construct a ceRNA network. The ssGSEA and CIBERSORT algorithms were utilized for immune cell infiltration analysis. Additionally, we validated our paclitaxel-related ceRNA regulatory axis at the gene expression level; functional experiments were conducted to explore the biological functions of the key genes. RESULTS: A total of 182 mRNAs, 13 miRNAs, and 53 lncRNAs were confirmed in the paclitaxel-related ceRNA network. In total, 6 mRNAs, 4 miRNAs, and 6 lncRNAs were identified to establish a risk signature and exhibited optimal prognostic effects. The mRNA signature can predict the abundance of immune cell infiltration and the sensitivity of different chemotherapeutic drugs and may also have a guiding effect in immune checkpoint therapy. A potential PART1/hsa-mir-21/SCRN1 axis was confirmed according to the ceRNA theory and was verified by qPCR. The results indicated that PART1 knockdown markedly increased hsa-mir-21 expression but inhibited SCRN1 expression, weakening the proliferation and migration abilities. CONCLUSIONS: We hypothesized that the paclitaxel-related ceRNA network strongly influences the innate mechanism, prognosis, and immune infiltration of pancreatic cancer. Our risk signatures can accurately predict survival outcomes and provide a clinical basis.
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spelling pubmed-90181662022-04-22 Construction of a paclitaxel-related competitive endogenous RNA network and identification of a potential regulatory axis in pancreatic cancer Lu, Si Yuan Hua, Jie Liu, Jiang Wei, Miao Yan Liang, Chen Meng, Qing Cai Zhang, Bo Yu, Xian Jun Wang, Wei Xu, Jin Transl Oncol Original Research BACKGROUND: Increasing numbers of studies have elucidated the role of competitive endogenous RNA (ceRNA) networks in carcinogenesis. However, the potential role of the paclitaxel-related ceRNA network in the innate mechanism and prognosis of pancreatic cancer has not been identified. METHODS: Comprehensive bioinformatics analyses were performed to identify drug-related miRNAs (DRmiRNAs), drug-related mRNAs (DRmRNAs) and drug-related lncRNAs (DRlncRNAs) and construct a ceRNA network. The ssGSEA and CIBERSORT algorithms were utilized for immune cell infiltration analysis. Additionally, we validated our paclitaxel-related ceRNA regulatory axis at the gene expression level; functional experiments were conducted to explore the biological functions of the key genes. RESULTS: A total of 182 mRNAs, 13 miRNAs, and 53 lncRNAs were confirmed in the paclitaxel-related ceRNA network. In total, 6 mRNAs, 4 miRNAs, and 6 lncRNAs were identified to establish a risk signature and exhibited optimal prognostic effects. The mRNA signature can predict the abundance of immune cell infiltration and the sensitivity of different chemotherapeutic drugs and may also have a guiding effect in immune checkpoint therapy. A potential PART1/hsa-mir-21/SCRN1 axis was confirmed according to the ceRNA theory and was verified by qPCR. The results indicated that PART1 knockdown markedly increased hsa-mir-21 expression but inhibited SCRN1 expression, weakening the proliferation and migration abilities. CONCLUSIONS: We hypothesized that the paclitaxel-related ceRNA network strongly influences the innate mechanism, prognosis, and immune infiltration of pancreatic cancer. Our risk signatures can accurately predict survival outcomes and provide a clinical basis. Neoplasia Press 2022-04-09 /pmc/articles/PMC9018166/ /pubmed/35413498 http://dx.doi.org/10.1016/j.tranon.2022.101419 Text en © 2022 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Lu, Si Yuan
Hua, Jie
Liu, Jiang
Wei, Miao Yan
Liang, Chen
Meng, Qing Cai
Zhang, Bo
Yu, Xian Jun
Wang, Wei
Xu, Jin
Construction of a paclitaxel-related competitive endogenous RNA network and identification of a potential regulatory axis in pancreatic cancer
title Construction of a paclitaxel-related competitive endogenous RNA network and identification of a potential regulatory axis in pancreatic cancer
title_full Construction of a paclitaxel-related competitive endogenous RNA network and identification of a potential regulatory axis in pancreatic cancer
title_fullStr Construction of a paclitaxel-related competitive endogenous RNA network and identification of a potential regulatory axis in pancreatic cancer
title_full_unstemmed Construction of a paclitaxel-related competitive endogenous RNA network and identification of a potential regulatory axis in pancreatic cancer
title_short Construction of a paclitaxel-related competitive endogenous RNA network and identification of a potential regulatory axis in pancreatic cancer
title_sort construction of a paclitaxel-related competitive endogenous rna network and identification of a potential regulatory axis in pancreatic cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018166/
https://www.ncbi.nlm.nih.gov/pubmed/35413498
http://dx.doi.org/10.1016/j.tranon.2022.101419
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