MicroRNA-190b Targets RFWD3 in Estrogen Receptor–Positive Breast Cancer
Background: In the year 2020, breast cancer was the most common form of cancer worldwide. Roughly 70% of breast cancers are estrogen receptor–positive (ER+). MicroRNA-190b (miR-190b) has previously been reported to be upregulated in ER+ breast cancers. Previously, we have demonstrated that miR-190b...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2024-03-01
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| Series: | Breast Cancer: Basic and Clinical Research |
| Online Access: | https://doi.org/10.1177/11782234241234771 |
| _version_ | 1827314579207618560 |
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| author | Elisabet Alexandra Frick Karen Kristjansdottir Snaedís Ragnarsdottir Arnar Ingi Vilhjalmsson Maria Rose Bustos Linda Vidarsdottir Thorkell Gudjonsson Stefan Sigurdsson |
| author_facet | Elisabet Alexandra Frick Karen Kristjansdottir Snaedís Ragnarsdottir Arnar Ingi Vilhjalmsson Maria Rose Bustos Linda Vidarsdottir Thorkell Gudjonsson Stefan Sigurdsson |
| author_sort | Elisabet Alexandra Frick |
| collection | DOAJ |
| description | Background: In the year 2020, breast cancer was the most common form of cancer worldwide. Roughly 70% of breast cancers are estrogen receptor–positive (ER+). MicroRNA-190b (miR-190b) has previously been reported to be upregulated in ER+ breast cancers. Previously, we have demonstrated that miR-190b is hypomethylated in ER+ breast cancers, potentially leading to its upregulation. Objectives: To further study the role of miR-190b in ER+ breast cancer and to identify its clinically relevant targets in breast cancer. Design: Patient cohort and cell line–based RNA-sequencing analysis. Methods: The Cancer Genome Atlas was used to obtain gene expression data and clinical information on patients with breast cancer. To identify messenger RNA (mRNA) targets for miR-190b, the ER+ breast cancer cell line T-47D was used to immunoprecipitate biotin-labeled miR-190b followed by RNA sequencing. Western blot was used to confirm miR-190b target. Patient survival based on miR-190b and selected target was studied using the Cancer Genome Atlas. Results: In this study, we confirm that miR-190b is overexpressed in breast cancer via differential expression analysis and show that high expression of miR-190b results in more favorable outcomes in Luminal A patients, hazard ratio (HR) = 0.29, 95% confidence interval [CI] = 0.12-0.71, P = .0063. MicroRNA-190b target analysis identified RING finger and WD repeat domain 3 (RFWD3) as one of miR-190b regulatory targets in ER+ breast cancer. Survival analysis of RFWD3 showed that elevated levels result in poorer overall survival in patients with Luminal A breast cancer (HR = 2.22, 95% CI = 1.33-3.71, P = .002). Gene ontology analysis of our sequencing results indicates that miR-190b may have a role in breast cancer development and/or tumorigenesis and that it may be a suitable tool in characterization between the ER+ subtypes, Luminal A, and Luminal B. Conclusions: We show that miR-190b targets RFWD3 in ER+ breast cancers leading to lower RFWD3 protein expression. Low levels of RFWD3 are associated with better outcomes in patients with Luminal A breast cancer but not in patients with Luminal B breast cancer. These findings provide novel insights into miR-190b role in breast cancer and that its clinical relevance is subtype specific. |
| first_indexed | 2024-04-24T22:37:20Z |
| format | Article |
| id | doaj.art-e0ec1cd6b9804f6db2ef983b9896a6c5 |
| institution | Directory Open Access Journal |
| issn | 1178-2234 |
| language | English |
| last_indexed | 2024-04-24T22:37:20Z |
| publishDate | 2024-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Breast Cancer: Basic and Clinical Research |
| spelling | doaj.art-e0ec1cd6b9804f6db2ef983b9896a6c52024-03-19T10:03:24ZengSAGE PublishingBreast Cancer: Basic and Clinical Research1178-22342024-03-011810.1177/11782234241234771MicroRNA-190b Targets RFWD3 in Estrogen Receptor–Positive Breast CancerElisabet Alexandra Frick0Karen Kristjansdottir1Snaedís Ragnarsdottir2Arnar Ingi Vilhjalmsson3Maria Rose Bustos4Linda Vidarsdottir5Thorkell Gudjonsson6Stefan Sigurdsson7Department of Biochemistry and Molecular Biology, Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, IcelandDepartment of Biochemistry and Molecular Biology, Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, IcelandDepartment of Biochemistry and Molecular Biology, Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, IcelandDepartment of Biochemistry and Molecular Biology, Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, IcelandDepartment of Biochemistry and Molecular Biology, Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, IcelandDepartment of Biochemistry and Molecular Biology, Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, IcelandBiotech Research & Innovation Centre, University of Copenhagen, Copenhagen, DenmarkDepartment of Biochemistry and Molecular Biology, Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, IcelandBackground: In the year 2020, breast cancer was the most common form of cancer worldwide. Roughly 70% of breast cancers are estrogen receptor–positive (ER+). MicroRNA-190b (miR-190b) has previously been reported to be upregulated in ER+ breast cancers. Previously, we have demonstrated that miR-190b is hypomethylated in ER+ breast cancers, potentially leading to its upregulation. Objectives: To further study the role of miR-190b in ER+ breast cancer and to identify its clinically relevant targets in breast cancer. Design: Patient cohort and cell line–based RNA-sequencing analysis. Methods: The Cancer Genome Atlas was used to obtain gene expression data and clinical information on patients with breast cancer. To identify messenger RNA (mRNA) targets for miR-190b, the ER+ breast cancer cell line T-47D was used to immunoprecipitate biotin-labeled miR-190b followed by RNA sequencing. Western blot was used to confirm miR-190b target. Patient survival based on miR-190b and selected target was studied using the Cancer Genome Atlas. Results: In this study, we confirm that miR-190b is overexpressed in breast cancer via differential expression analysis and show that high expression of miR-190b results in more favorable outcomes in Luminal A patients, hazard ratio (HR) = 0.29, 95% confidence interval [CI] = 0.12-0.71, P = .0063. MicroRNA-190b target analysis identified RING finger and WD repeat domain 3 (RFWD3) as one of miR-190b regulatory targets in ER+ breast cancer. Survival analysis of RFWD3 showed that elevated levels result in poorer overall survival in patients with Luminal A breast cancer (HR = 2.22, 95% CI = 1.33-3.71, P = .002). Gene ontology analysis of our sequencing results indicates that miR-190b may have a role in breast cancer development and/or tumorigenesis and that it may be a suitable tool in characterization between the ER+ subtypes, Luminal A, and Luminal B. Conclusions: We show that miR-190b targets RFWD3 in ER+ breast cancers leading to lower RFWD3 protein expression. Low levels of RFWD3 are associated with better outcomes in patients with Luminal A breast cancer but not in patients with Luminal B breast cancer. These findings provide novel insights into miR-190b role in breast cancer and that its clinical relevance is subtype specific.https://doi.org/10.1177/11782234241234771 |
| spellingShingle | Elisabet Alexandra Frick Karen Kristjansdottir Snaedís Ragnarsdottir Arnar Ingi Vilhjalmsson Maria Rose Bustos Linda Vidarsdottir Thorkell Gudjonsson Stefan Sigurdsson MicroRNA-190b Targets RFWD3 in Estrogen Receptor–Positive Breast Cancer Breast Cancer: Basic and Clinical Research |
| title | MicroRNA-190b Targets RFWD3 in Estrogen Receptor–Positive Breast Cancer |
| title_full | MicroRNA-190b Targets RFWD3 in Estrogen Receptor–Positive Breast Cancer |
| title_fullStr | MicroRNA-190b Targets RFWD3 in Estrogen Receptor–Positive Breast Cancer |
| title_full_unstemmed | MicroRNA-190b Targets RFWD3 in Estrogen Receptor–Positive Breast Cancer |
| title_short | MicroRNA-190b Targets RFWD3 in Estrogen Receptor–Positive Breast Cancer |
| title_sort | microrna 190b targets rfwd3 in estrogen receptor positive breast cancer |
| url | https://doi.org/10.1177/11782234241234771 |
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