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Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues

Breast cancer is the most common neoplasm among females. Estrogen receptor (ESR) signaling has a prominent impact in the pathogenesis of breast cancer. Among the transcription factors associated with ESR signaling, FOXM1, GATA3, FOXA1 and ESR1 have been suggested as a candidate in the pathogenesis o...

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Autores principales: Hassani, Bita, Taheri, Mohammad, Asgari, Yazdan, Zekri, Ali, Sattari, Ali, Ghafouri-Fard, Soudeh, Pouresmaeili, Farkhondeh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171254/
https://www.ncbi.nlm.nih.gov/pubmed/34094972
http://dx.doi.org/10.3389/fonc.2021.671418
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author Hassani, Bita
Taheri, Mohammad
Asgari, Yazdan
Zekri, Ali
Sattari, Ali
Ghafouri-Fard, Soudeh
Pouresmaeili, Farkhondeh
author_facet Hassani, Bita
Taheri, Mohammad
Asgari, Yazdan
Zekri, Ali
Sattari, Ali
Ghafouri-Fard, Soudeh
Pouresmaeili, Farkhondeh
author_sort Hassani, Bita
collection PubMed
description Breast cancer is the most common neoplasm among females. Estrogen receptor (ESR) signaling has a prominent impact in the pathogenesis of breast cancer. Among the transcription factors associated with ESR signaling, FOXM1, GATA3, FOXA1 and ESR1 have been suggested as a candidate in the pathogenesis of this neoplasm. In the current project, we have designed an in silico approach to find long non-coding RNAs (lncRNAs) that regulate these transcription factors. Then, we used clinical samples to carry out validation of our in silico findings. Our systems biology method led to the identification of APTR, AC144450.1, linc00663, ZNF337.AS1, and RAMP2.AS1 lncRNAs. Subsequently, we assessed the expression of these genes in breast cancer tissues compared with the adjacent non-cancerous tissues (ANCTs). Expression of GATA3 was significantly higher in breast cancer tissues compared with ANCTs (Ratio of mean expressions (RME) = 4.99, P value = 3.12E−04). Moreover, expression levels of APTR, AC144450.1, and ZNF337.AS1 were elevated in breast cancer tissues compared with control tissues (RME = 2.27, P value = 5.40E−03; Ratio of mean expressions = 615.95, P value = 7.39E−19 and RME = 1.78, P value = 3.40E−02, respectively). On the other hand, the expression of RAMP2.AS1 was lower in breast cancer tissues than controls (RME = 0.31, P value = 1.87E−03). Expression levels of FOXA1, ESR1, and FOXM1 and linc00663 were not significantly different between the two sets of samples. Expression of GATA3 was significantly associated with stage (P value = 4.77E−02). Moreover, expressions of FOXA1 and RAMP2.AS1 were associated with the mitotic rate (P values = 2.18E−02 and 1.77E−02, respectively). Finally, expressions of FOXM1 and ZNF337.AS1 were associated with breastfeeding duration (P values = 3.88E−02 and 4.33E−02, respectively). Based on the area under receiver operating characteristics curves, AC144450.1 had the optimal diagnostic power in differentiating between cancerous and non-cancerous tissues (AUC = 0.95, Sensitivity = 0.90, Specificity = 0.96). The combination of expression levels of all genes slightly increased the diagnostic power (AUC = 0.96). While there were several significant pairwise correlations between expression levels of genes in non-tumoral tissues, the most robust correlation was identified between linc00663 and RAMP2.AS1 (r = 0.61, P value = 3.08E−8). In the breast cancer tissues, the strongest correlations were reported between FOXM1/ZNF337.AS1 and FOXM1/RAMP2.AS1 pairs (r = 0.51, P value = 4.79E−5 and r = 0.51, P value = 6.39E−5, respectively). The current investigation suggests future assessment of the functional role of APTR, AC144450.1 and ZNF337.AS1 in the development of breast neoplasms.
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spelling pubmed-81712542021-06-03 Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues Hassani, Bita Taheri, Mohammad Asgari, Yazdan Zekri, Ali Sattari, Ali Ghafouri-Fard, Soudeh Pouresmaeili, Farkhondeh Front Oncol Oncology Breast cancer is the most common neoplasm among females. Estrogen receptor (ESR) signaling has a prominent impact in the pathogenesis of breast cancer. Among the transcription factors associated with ESR signaling, FOXM1, GATA3, FOXA1 and ESR1 have been suggested as a candidate in the pathogenesis of this neoplasm. In the current project, we have designed an in silico approach to find long non-coding RNAs (lncRNAs) that regulate these transcription factors. Then, we used clinical samples to carry out validation of our in silico findings. Our systems biology method led to the identification of APTR, AC144450.1, linc00663, ZNF337.AS1, and RAMP2.AS1 lncRNAs. Subsequently, we assessed the expression of these genes in breast cancer tissues compared with the adjacent non-cancerous tissues (ANCTs). Expression of GATA3 was significantly higher in breast cancer tissues compared with ANCTs (Ratio of mean expressions (RME) = 4.99, P value = 3.12E−04). Moreover, expression levels of APTR, AC144450.1, and ZNF337.AS1 were elevated in breast cancer tissues compared with control tissues (RME = 2.27, P value = 5.40E−03; Ratio of mean expressions = 615.95, P value = 7.39E−19 and RME = 1.78, P value = 3.40E−02, respectively). On the other hand, the expression of RAMP2.AS1 was lower in breast cancer tissues than controls (RME = 0.31, P value = 1.87E−03). Expression levels of FOXA1, ESR1, and FOXM1 and linc00663 were not significantly different between the two sets of samples. Expression of GATA3 was significantly associated with stage (P value = 4.77E−02). Moreover, expressions of FOXA1 and RAMP2.AS1 were associated with the mitotic rate (P values = 2.18E−02 and 1.77E−02, respectively). Finally, expressions of FOXM1 and ZNF337.AS1 were associated with breastfeeding duration (P values = 3.88E−02 and 4.33E−02, respectively). Based on the area under receiver operating characteristics curves, AC144450.1 had the optimal diagnostic power in differentiating between cancerous and non-cancerous tissues (AUC = 0.95, Sensitivity = 0.90, Specificity = 0.96). The combination of expression levels of all genes slightly increased the diagnostic power (AUC = 0.96). While there were several significant pairwise correlations between expression levels of genes in non-tumoral tissues, the most robust correlation was identified between linc00663 and RAMP2.AS1 (r = 0.61, P value = 3.08E−8). In the breast cancer tissues, the strongest correlations were reported between FOXM1/ZNF337.AS1 and FOXM1/RAMP2.AS1 pairs (r = 0.51, P value = 4.79E−5 and r = 0.51, P value = 6.39E−5, respectively). The current investigation suggests future assessment of the functional role of APTR, AC144450.1 and ZNF337.AS1 in the development of breast neoplasms. Frontiers Media S.A. 2021-05-19 /pmc/articles/PMC8171254/ /pubmed/34094972 http://dx.doi.org/10.3389/fonc.2021.671418 Text en Copyright © 2021 Hassani, Taheri, Asgari, Zekri, Sattari, Ghafouri-Fard and Pouresmaeili https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Hassani, Bita
Taheri, Mohammad
Asgari, Yazdan
Zekri, Ali
Sattari, Ali
Ghafouri-Fard, Soudeh
Pouresmaeili, Farkhondeh
Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues
title Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues
title_full Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues
title_fullStr Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues
title_full_unstemmed Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues
title_short Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues
title_sort expression analysis of long non-coding rnas related with foxm1, gata3, foxa1 and esr1 in breast tissues
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171254/
https://www.ncbi.nlm.nih.gov/pubmed/34094972
http://dx.doi.org/10.3389/fonc.2021.671418
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