Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer
Our understanding of the function of long non-coding RNAs (lncRNAs) in health and disease states has evolved over the past decades due to the many advances in genome research. In the current study, we characterized the lncRNA transcriptome enriched in triple-negative breast cancer (TNBC, n = 42) and...
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| Format: | Article |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1149860/full |
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| author | Radhakrishnan Vishnubalaji Nehad M. Alajez Nehad M. Alajez |
| author_facet | Radhakrishnan Vishnubalaji Nehad M. Alajez Nehad M. Alajez |
| author_sort | Radhakrishnan Vishnubalaji |
| collection | DOAJ |
| description | Our understanding of the function of long non-coding RNAs (lncRNAs) in health and disease states has evolved over the past decades due to the many advances in genome research. In the current study, we characterized the lncRNA transcriptome enriched in triple-negative breast cancer (TNBC, n = 42) and estrogen receptor (ER+, n = 42) breast cancer compared to normal breast tissue (n = 56). Given the aggressive nature of TNBC, our data revealed selective enrichment of 57 lncRNAs in TNBC. Among those, AC099850.4 lncRNA was chosen for further investigation where it exhibited elevated expression, which was further confirmed in a second TNBC cohort (n = 360) where its expression correlated with a worse prognosis. Network analysis of AC099850.4high TNBC highlighted enrichment in functional categories indicative of cell cycle activation and mitosis. Ingenuity pathway analysis on the differentially expressed genes in AC099850.4high TNBC revealed the activation of the canonical kinetochore metaphase signaling pathway, pyridoxal 5'-phosphate salvage pathway, and salvage pathways of pyrimidine ribonucleotides. Additionally, upstream regulator analysis predicted the activation of several upstream regulator networks including CKAP2L, FOXM1, RABL6, PCLAF, and MITF, while upstream regulator networks of TP53, NUPR1, TRPS1, and CDKN1A were suppressed. Interestingly, elevated expression of AC099850.4 correlated with worse short-term relapse-free survival (log-rank p = 0.01). Taken together, our data are the first to reveal AC099850.4 as an unfavorable prognostic marker in TNBC, associated with more aggressive clinicopathological features, and suggest its potential utilization as a prognostic biomarker and therapeutic target in TNBC. |
| first_indexed | 2024-03-12T11:49:17Z |
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| language | English |
| last_indexed | 2024-03-12T11:49:17Z |
| publishDate | 2023-08-01 |
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| series | Frontiers in Medicine |
| spelling | doaj.art-1033c06730de48218c5c4313f64e70e62023-08-31T11:24:13ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-08-011010.3389/fmed.2023.11498601149860Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancerRadhakrishnan Vishnubalaji0Nehad M. Alajez1Nehad M. Alajez2Translational Cancer and Immunity Center (TCIC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, QatarTranslational Cancer and Immunity Center (TCIC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, QatarCollege of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, QatarOur understanding of the function of long non-coding RNAs (lncRNAs) in health and disease states has evolved over the past decades due to the many advances in genome research. In the current study, we characterized the lncRNA transcriptome enriched in triple-negative breast cancer (TNBC, n = 42) and estrogen receptor (ER+, n = 42) breast cancer compared to normal breast tissue (n = 56). Given the aggressive nature of TNBC, our data revealed selective enrichment of 57 lncRNAs in TNBC. Among those, AC099850.4 lncRNA was chosen for further investigation where it exhibited elevated expression, which was further confirmed in a second TNBC cohort (n = 360) where its expression correlated with a worse prognosis. Network analysis of AC099850.4high TNBC highlighted enrichment in functional categories indicative of cell cycle activation and mitosis. Ingenuity pathway analysis on the differentially expressed genes in AC099850.4high TNBC revealed the activation of the canonical kinetochore metaphase signaling pathway, pyridoxal 5'-phosphate salvage pathway, and salvage pathways of pyrimidine ribonucleotides. Additionally, upstream regulator analysis predicted the activation of several upstream regulator networks including CKAP2L, FOXM1, RABL6, PCLAF, and MITF, while upstream regulator networks of TP53, NUPR1, TRPS1, and CDKN1A were suppressed. Interestingly, elevated expression of AC099850.4 correlated with worse short-term relapse-free survival (log-rank p = 0.01). Taken together, our data are the first to reveal AC099850.4 as an unfavorable prognostic marker in TNBC, associated with more aggressive clinicopathological features, and suggest its potential utilization as a prognostic biomarker and therapeutic target in TNBC.https://www.frontiersin.org/articles/10.3389/fmed.2023.1149860/fullnoncoding RNAlncRNAAC099850.4biomarkerstriple negative breast cancerprognosis |
| spellingShingle | Radhakrishnan Vishnubalaji Nehad M. Alajez Nehad M. Alajez Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer Frontiers in Medicine noncoding RNA lncRNA AC099850.4 biomarkers triple negative breast cancer prognosis |
| title | Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer |
| title_full | Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer |
| title_fullStr | Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer |
| title_full_unstemmed | Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer |
| title_short | Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer |
| title_sort | long non coding rna ac099850 4 correlates with advanced disease state and predicts worse prognosis in triple negative breast cancer |
| topic | noncoding RNA lncRNA AC099850.4 biomarkers triple negative breast cancer prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1149860/full |
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