期刊
ONCOTARGET
卷 8, 期 16, 页码 25963-25976出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15657
关键词
breast cancer; progesterone receptor; microRNA; miR-181a; miR-23a
资金
- Israel Cancer Research Fund (ICRF)
- Research Career Development Award (RCDA)
- Wolfson Family Charitable Fund
- Earlier.org - Friends for an Earlier Breast Cancer Test
- Claire and Amedee Maratier Institute for the Study of Blindness and Visual Disorders
- I-CORE Program of the Planning and Budgeting Committee
- Israel Science Foundation [41/11]
- Israeli Ministry of Defense, Office of Defense for Chemical, Biological, Radiological and Nuclear (CBRN) Defense
- Foundation Fighting Blindness
- Saban Family Foundation, Melanoma Research Alliance
- Binational Science Foundation (BSF)
- Israel Cancer Research Fund (ICRF) Acceleration Grant
- Israel Cancer Association (ICA)
- Kateznik K. Association Holocaust
- Margot Stoltz Foundation through the Faculty of Medicine grants of Tel-Aviv University
- Varda and Boaz Dotan Research Center in Hemato-Oncology, Idea Grant
- 'Lirot' Association and the Consortium for Mapping Retinal Degeneration Disorders in Israel
- Interdisciplinary grant of the Israeli Ministry of Science, Technology and Space on the Science, Technology and Innovation for the Third Age
- Edmond J. Safra Center for Ethics at Tel Aviv University
- Check Point Institute for Information Security
- Joint Core Program of Research on the Molecular Basis of Human Disease
- Italian Ministry of Foreign Affairs
- Israel Science Foundation (ISF) [1852/16]
- The Edmond J. Safra Center for Bioinformatics at Tel Aviv University
Hormone receptor status is of significant value when deciding on anti-estrogenic adjuvant therapy for breast cancer tumors. However, while estrogen receptor (ER) regulation was intensively studied, the regulation of progesterone receptor (PR) levels has not been extensively investigated. MicroRNAs (miRNAs, miRs) are post-transcriptional negative regulators of gene expression involved in diverse cellular processes. The aim of this study was to identify miRNAs that regulate PR in breast cancer. We mapped potential miRNA binding sites for miR-181a, miR-23a and miR-26b on PR mRNA and demonstrated a direct regulation of PR by these three miRNAs by in-vitro Luciferase binding assays. Over-expression of each miRNA in MCF-7 cells resulted in a reduction in the expression levels of PR mRNA. Then, expression levels of these miRNAs were measured in Formalin-Fixed, Paraffin-Embedded (FFPE) samples of 29 ER-positive breast cancer tumors and adjacent normal breast tissues. A significant reciprocal correlation between PR mRNA and the miRNA levels were identified suggesting a role for miR-181a, miR-23a and miR-26b in PR regulation in breast cancer. Moreover, the average expression fold-changes of the three miRNAs between cancerous and normal tissues displayed an opposite trend when analyzing according to Immuno-histochemistry (IHC) status. Furthermore, miR-181a and miR-26b were found to be over-expressed in most tumor tissues supporting their role in ER-positive breast cancer development. We conclude that miR-181a, miR-23a and miR-26b act as negative regulators of PR expression in ER-positive breast cancer. The diagnostic and prognostic potential of these miRNAs in breast cancer should be further evaluated.
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