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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.671418/full |
| _version_ | 1819086095778840576 |
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| author | Bita Hassani Mohammad Taheri Yazdan Asgari Ali Zekri Ali Sattari Soudeh Ghafouri-Fard Farkhondeh Pouresmaeili |
| author_facet | Bita Hassani Mohammad Taheri Yazdan Asgari Ali Zekri Ali Sattari Soudeh Ghafouri-Fard Farkhondeh Pouresmaeili |
| author_sort | Bita Hassani |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T21:14:48Z |
| format | Article |
| id | doaj.art-6d0d371d2488460a8e25a408cdb05258 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T21:14:48Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-6d0d371d2488460a8e25a408cdb052582022-12-21T18:50:02ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.671418671418Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast TissuesBita Hassani0Mohammad Taheri1Yazdan Asgari2Ali Zekri3Ali Sattari4Soudeh Ghafouri-Fard5Farkhondeh Pouresmaeili6Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, IranUrology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Medical Genetics and Molecular biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, IranDepartment of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, IranMen’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranMen’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranBreast 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.671418/fullbreast cancerlncRNAsFOXM1/GATA3/FOXA1/ESR1 axisAPTRAC144450.1linc00663 |
| spellingShingle | Bita Hassani Mohammad Taheri Yazdan Asgari Ali Zekri Ali Sattari Soudeh Ghafouri-Fard Farkhondeh Pouresmaeili Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues Frontiers in Oncology breast cancer lncRNAs FOXM1/GATA3/FOXA1/ESR1 axis APTR AC144450.1 linc00663 |
| 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 | breast cancer lncRNAs FOXM1/GATA3/FOXA1/ESR1 axis APTR AC144450.1 linc00663 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.671418/full |
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