Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer
Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, representing the most aggressive breast cancer (BC) subtype with limited treatment options due to a lack of estrogen receptor alpha (ERα), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2/neu) expression....
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MDPI AG
2020-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/4/874 |
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| author | Elena Alexandrova Jessica Lamberti Pasquale Saggese Giovanni Pecoraro Domenico Memoli Valeria Mirici Cappa Maria Ravo Roberta Iorio Roberta Tarallo Francesca Rizzo Francesca Collina Monica Cantile Maurizio Di Bonito Gerardo Botti Giovanni Nassa Alessandro Weisz Giorgio Giurato |
| author_facet | Elena Alexandrova Jessica Lamberti Pasquale Saggese Giovanni Pecoraro Domenico Memoli Valeria Mirici Cappa Maria Ravo Roberta Iorio Roberta Tarallo Francesca Rizzo Francesca Collina Monica Cantile Maurizio Di Bonito Gerardo Botti Giovanni Nassa Alessandro Weisz Giorgio Giurato |
| author_sort | Elena Alexandrova |
| collection | DOAJ |
| description | Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, representing the most aggressive breast cancer (BC) subtype with limited treatment options due to a lack of estrogen receptor alpha (ERα), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2/neu) expression. Estrogen receptor beta (ERβ) is present in a fraction of TNBC patients, where its expression correlates with improved patient outcomes, supported by the fact that it exerts oncosuppressive effects in TNBC cell models in vitro. ERβ is involved in microRNA-mediated regulation of gene expression in hormone-responsive BC cells and could mediate its actions through small noncoding RNAs (sncRNAs) in TNBCs also. To verify this possibility, smallRNA sequencing was performed on three ERβ-expressing cell lines from different TNBC molecular subtypes. Several sncRNAs resulted modulated by ERβ, with a subset being regulated in a tumor subtype-independent manner. Interestingly, sncRNA profiling of 12 ERβ+and 32 ERβ− primary TNBC biopsies identified 7 microRNAs, 1 PIWI-interacting RNA (piRNA), and 1 transfer RNA (tRNA) differentially expressed in ERβ+ compared to ERβ− tumors and cell lines. Among them, miR-181a-5p was found to be overexpressed in ERβ+ tumors and predicted target key components of the cholesterol biosynthesis pathway previously found to be inhibited by ERβ in TNBC cells. |
| first_indexed | 2024-03-10T20:42:23Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T20:42:23Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-cffd2d44b5da4d709a4b159027f267062023-11-19T20:36:25ZengMDPI AGCells2073-44092020-04-019487410.3390/cells9040874Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast CancerElena Alexandrova0Jessica Lamberti1Pasquale Saggese2Giovanni Pecoraro3Domenico Memoli4Valeria Mirici Cappa5Maria Ravo6Roberta Iorio7Roberta Tarallo8Francesca Rizzo9Francesca Collina10Monica Cantile11Maurizio Di Bonito12Gerardo Botti13Giovanni Nassa14Alessandro Weisz15Giorgio Giurato16Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyGenomix4Life Srl, 84081 Baronissi, ItalyLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyPathology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, ItalyPathology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, ItalyPathology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, ItalyScientific Direction, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, ItalyLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, 84081 Baronissi, ItalyTriple-negative breast cancer (TNBC) is a highly heterogeneous disease, representing the most aggressive breast cancer (BC) subtype with limited treatment options due to a lack of estrogen receptor alpha (ERα), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2/neu) expression. Estrogen receptor beta (ERβ) is present in a fraction of TNBC patients, where its expression correlates with improved patient outcomes, supported by the fact that it exerts oncosuppressive effects in TNBC cell models in vitro. ERβ is involved in microRNA-mediated regulation of gene expression in hormone-responsive BC cells and could mediate its actions through small noncoding RNAs (sncRNAs) in TNBCs also. To verify this possibility, smallRNA sequencing was performed on three ERβ-expressing cell lines from different TNBC molecular subtypes. Several sncRNAs resulted modulated by ERβ, with a subset being regulated in a tumor subtype-independent manner. Interestingly, sncRNA profiling of 12 ERβ+and 32 ERβ− primary TNBC biopsies identified 7 microRNAs, 1 PIWI-interacting RNA (piRNA), and 1 transfer RNA (tRNA) differentially expressed in ERβ+ compared to ERβ− tumors and cell lines. Among them, miR-181a-5p was found to be overexpressed in ERβ+ tumors and predicted target key components of the cholesterol biosynthesis pathway previously found to be inhibited by ERβ in TNBC cells.https://www.mdpi.com/2073-4409/9/4/874triple-negative breast cancerestrogen receptor betasmall non-coding RNAsmicroRNAcholesterol biosynthesis |
| spellingShingle | Elena Alexandrova Jessica Lamberti Pasquale Saggese Giovanni Pecoraro Domenico Memoli Valeria Mirici Cappa Maria Ravo Roberta Iorio Roberta Tarallo Francesca Rizzo Francesca Collina Monica Cantile Maurizio Di Bonito Gerardo Botti Giovanni Nassa Alessandro Weisz Giorgio Giurato Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer Cells triple-negative breast cancer estrogen receptor beta small non-coding RNAs microRNA cholesterol biosynthesis |
| title | Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer |
| title_full | Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer |
| title_fullStr | Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer |
| title_full_unstemmed | Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer |
| title_short | Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer |
| title_sort | small non coding rna profiling identifies mir 181a 5p as a mediator of estrogen receptor beta induced inhibition of cholesterol biosynthesis in triple negative breast cancer |
| topic | triple-negative breast cancer estrogen receptor beta small non-coding RNAs microRNA cholesterol biosynthesis |
| url | https://www.mdpi.com/2073-4409/9/4/874 |
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