WWTR1-AS1 LncRNA as a Novel Potential Diagnostic and Prognostic Biomarker in Breast Cancer

Breast cancer is the most lethal form of cancer in women, and patients face serious health risks. Long non-coding RNAs are involved in a variety of regulatory processes and can influence cancers development at different levels. This study aimed to introduce a central regulatory lncRNA based on diffe...

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Main Authors: Mohadese Safabakhsh, Sohrab Boozarpour, Kamran Ghaedi, Mina Lashkarboloki, Shaaban Ghalandarayeshi
Format: Article
Language:English
Published: University of Mazandaran 2024-02-01
Series:Journal of Genetic Resources
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Online Access:https://sc.journals.umz.ac.ir/article_4942_3995f757769a11ec58f0f292f8ac4e0c.pdf
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author Mohadese Safabakhsh
Sohrab Boozarpour
Kamran Ghaedi
Mina Lashkarboloki
Shaaban Ghalandarayeshi
author_facet Mohadese Safabakhsh
Sohrab Boozarpour
Kamran Ghaedi
Mina Lashkarboloki
Shaaban Ghalandarayeshi
author_sort Mohadese Safabakhsh
collection DOAJ
description Breast cancer is the most lethal form of cancer in women, and patients face serious health risks. Long non-coding RNAs are involved in a variety of regulatory processes and can influence cancers development at different levels. This study aimed to introduce a central regulatory lncRNA based on differentially expressed proteins in breast cancer and evaluate its expression level in breast tissues. In this study, proteomic data was obtained from ProteomeXchange and then differentially expressed proteins were detected. The Enrichr database was used to identify the regulatory factors of differentially expressed proteins, and functional enrichment analysis was used to demonstrate key signaling pathways and biological processes. Eventually, a lncRNA with the highest rank in the central hub was chosen, and its expression level was measured by RT-qPCR in 15 breast cancer tissues and their adjacent nontumor tissues. Proteomic analysis recognized 1149 differential expressed proteins in breast cancer with regulatory agents consisting of 76 TFs, 61 kinases, 366 miRNAs, and 162 lncRNAs. A multi-regulatory network with 1811 nodes and 4022 edges was constructed based on differentially expressed proteins and their associated elements. In addition, these regulatory elements were related to three biological functions and 11 pathways. Finally, bioinformatic analysis identified lncRNA WWTR1-AS1 as having the highest node score involved in different mechanisms. Functional experiments confirmed that the expression level of the lncRNA WWTR1-AS1 was significantly increased in breast cancer patients.  ROC analysis suggested that this lncRNA can be used as a reliable biomarker. Our data provide evidence that the lncRNA WWTR1-AS1 is an effective factor in the regulation of DEPs, is associated with malignant features in breast cancer, and might be useful as a prognostic marker in Breast cancer.
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spelling doaj-art-22e69483248e4165bb5dd77a16385eef2025-01-27T06:11:19ZengUniversity of MazandaranJournal of Genetic Resources2423-42572588-25892024-02-01101667510.22080/jgr.2024.26832.13854942WWTR1-AS1 LncRNA as a Novel Potential Diagnostic and Prognostic Biomarker in Breast CancerMohadese Safabakhsh0Sohrab Boozarpour1Kamran Ghaedi2Mina Lashkarboloki3Shaaban Ghalandarayeshi4Department of Biology, Faculty of Basic Sciences, Gonbad Kavous University, Gonbad Kavous, Golestan, IranDepartment of Biology, Faculty of Basic Sciences, Gonbad Kavous University, Gonbad Kavous, Golestan, IranDepartment of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, IranDepartment of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IranDepartment of Mathematics and Statistics, Faculty of Basic Sciences, Gonbad Kavous University, Gonbad Kavous, Golestan, IranBreast cancer is the most lethal form of cancer in women, and patients face serious health risks. Long non-coding RNAs are involved in a variety of regulatory processes and can influence cancers development at different levels. This study aimed to introduce a central regulatory lncRNA based on differentially expressed proteins in breast cancer and evaluate its expression level in breast tissues. In this study, proteomic data was obtained from ProteomeXchange and then differentially expressed proteins were detected. The Enrichr database was used to identify the regulatory factors of differentially expressed proteins, and functional enrichment analysis was used to demonstrate key signaling pathways and biological processes. Eventually, a lncRNA with the highest rank in the central hub was chosen, and its expression level was measured by RT-qPCR in 15 breast cancer tissues and their adjacent nontumor tissues. Proteomic analysis recognized 1149 differential expressed proteins in breast cancer with regulatory agents consisting of 76 TFs, 61 kinases, 366 miRNAs, and 162 lncRNAs. A multi-regulatory network with 1811 nodes and 4022 edges was constructed based on differentially expressed proteins and their associated elements. In addition, these regulatory elements were related to three biological functions and 11 pathways. Finally, bioinformatic analysis identified lncRNA WWTR1-AS1 as having the highest node score involved in different mechanisms. Functional experiments confirmed that the expression level of the lncRNA WWTR1-AS1 was significantly increased in breast cancer patients.  ROC analysis suggested that this lncRNA can be used as a reliable biomarker. Our data provide evidence that the lncRNA WWTR1-AS1 is an effective factor in the regulation of DEPs, is associated with malignant features in breast cancer, and might be useful as a prognostic marker in Breast cancer.https://sc.journals.umz.ac.ir/article_4942_3995f757769a11ec58f0f292f8ac4e0c.pdfbreast cancercomputational biologygene regulatory networkslong noncoding rnaproteomics
spellingShingle Mohadese Safabakhsh
Sohrab Boozarpour
Kamran Ghaedi
Mina Lashkarboloki
Shaaban Ghalandarayeshi
WWTR1-AS1 LncRNA as a Novel Potential Diagnostic and Prognostic Biomarker in Breast Cancer
Journal of Genetic Resources
breast cancer
computational biology
gene regulatory networks
long noncoding rna
proteomics
title WWTR1-AS1 LncRNA as a Novel Potential Diagnostic and Prognostic Biomarker in Breast Cancer
title_full WWTR1-AS1 LncRNA as a Novel Potential Diagnostic and Prognostic Biomarker in Breast Cancer
title_fullStr WWTR1-AS1 LncRNA as a Novel Potential Diagnostic and Prognostic Biomarker in Breast Cancer
title_full_unstemmed WWTR1-AS1 LncRNA as a Novel Potential Diagnostic and Prognostic Biomarker in Breast Cancer
title_short WWTR1-AS1 LncRNA as a Novel Potential Diagnostic and Prognostic Biomarker in Breast Cancer
title_sort wwtr1 as1 lncrna as a novel potential diagnostic and prognostic biomarker in breast cancer
topic breast cancer
computational biology
gene regulatory networks
long noncoding rna
proteomics
url https://sc.journals.umz.ac.ir/article_4942_3995f757769a11ec58f0f292f8ac4e0c.pdf
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