Differential expression, function and prognostic value of miR-17–92 cluster in ER-positive and triple-negative breast cancer
Recent evidence has shown that the miR-17–92 cluster can function either as oncogene or tumor suppressor in human cancers. The function of miR-17–92 in subtypes of breast cancer remains largely unknown. The expression of miR-17–92 is elevated in triple negative breast cancer (TNBC) but reduced in es...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Cancer Treatment and Research Communications |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468294220300599 |
| _version_ | 1818871629712719872 |
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| author | Muhammad Mosaraf Hossain Afrin Sultana David Barua Md Nahidul Islam Ananya Gupta Sanjeev Gupta |
| author_facet | Muhammad Mosaraf Hossain Afrin Sultana David Barua Md Nahidul Islam Ananya Gupta Sanjeev Gupta |
| author_sort | Muhammad Mosaraf Hossain |
| collection | DOAJ |
| description | Recent evidence has shown that the miR-17–92 cluster can function either as oncogene or tumor suppressor in human cancers. The function of miR-17–92 in subtypes of breast cancer remains largely unknown. The expression of miR-17–92 is elevated in triple negative breast cancer (TNBC) but reduced in estrogen receptor (ER)-positive breast cancer (ERPBC). We show that increased expression of miRNAs belonging to the miR-17–92 cluster is associated with poor outcome in TNBC, whereas the expression of miR-17–92 miRNAs is with good outcome in ERPBC. We show that ectopic expression of miR-17–92 inhibited cell growth and invasion of ER-positive and HER2-enriched cells. On the contrary, miR-17–92 expression enhanced cell growth and invasion of TNBC cells. Further, we found that miR-17–92 expression sensitized MCF7 cells to chemotherapeutic compounds, whereas it rendered SKBR3 cells resistant to them. We found that expression of ADORA1 was reduced by miR-17–92-expressing breast cancer cells, specifically in ERPBC. We observed an inverse correlation between the expression of ADORA1 and miR-17–92 in human breast cancer. Treatment with DPCPX, a selective ADORA1 antagonist, abolished the difference in the growth of control and miR-17–92 overexpressing MCF7 cells and identified ADORA1 as a key functional target of miR-17–92 in ERPBC. Furthermore, increased expression of ADORA1 in ERPBC is associated with a poor outcome. Our observations underscore the context-dependent role of miR-17–92 in breast cancer subtypes and suggest that miR-17–92 could serve as novel prognostic markers in breast cancer. |
| first_indexed | 2024-12-19T12:25:58Z |
| format | Article |
| id | doaj.art-daf3ca6ced6749579d32a5ab48f370eb |
| institution | Directory Open Access Journal |
| issn | 2468-2942 |
| language | English |
| last_indexed | 2024-12-19T12:25:58Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cancer Treatment and Research Communications |
| spelling | doaj.art-daf3ca6ced6749579d32a5ab48f370eb2022-12-21T20:21:34ZengElsevierCancer Treatment and Research Communications2468-29422020-01-0125100224Differential expression, function and prognostic value of miR-17–92 cluster in ER-positive and triple-negative breast cancerMuhammad Mosaraf Hossain0Afrin Sultana1David Barua2Md Nahidul Islam3Ananya Gupta4Sanjeev Gupta5Discipline of Pathology, Cancer Progression and Treatment Research Group, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, IrelandDiscipline of Pathology, Cancer Progression and Treatment Research Group, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, IrelandDiscipline of Pathology, Cancer Progression and Treatment Research Group, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, IrelandDiscipline of Biochemistry, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland; Regenerative Medicine Institute, Biomedical Sciences Building, School of Medicine, National University of Ireland Galway, Galway, IrelandDiscipline of Physiology, Human Biology Building, School of Medicine, National University of Ireland Galway, Galway, IrelandDiscipline of Pathology, Cancer Progression and Treatment Research Group, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland; Corresponding author: Sanjeev Gupta, PhD, School of Medicine, NUI Galway, Galway, IrelandRecent evidence has shown that the miR-17–92 cluster can function either as oncogene or tumor suppressor in human cancers. The function of miR-17–92 in subtypes of breast cancer remains largely unknown. The expression of miR-17–92 is elevated in triple negative breast cancer (TNBC) but reduced in estrogen receptor (ER)-positive breast cancer (ERPBC). We show that increased expression of miRNAs belonging to the miR-17–92 cluster is associated with poor outcome in TNBC, whereas the expression of miR-17–92 miRNAs is with good outcome in ERPBC. We show that ectopic expression of miR-17–92 inhibited cell growth and invasion of ER-positive and HER2-enriched cells. On the contrary, miR-17–92 expression enhanced cell growth and invasion of TNBC cells. Further, we found that miR-17–92 expression sensitized MCF7 cells to chemotherapeutic compounds, whereas it rendered SKBR3 cells resistant to them. We found that expression of ADORA1 was reduced by miR-17–92-expressing breast cancer cells, specifically in ERPBC. We observed an inverse correlation between the expression of ADORA1 and miR-17–92 in human breast cancer. Treatment with DPCPX, a selective ADORA1 antagonist, abolished the difference in the growth of control and miR-17–92 overexpressing MCF7 cells and identified ADORA1 as a key functional target of miR-17–92 in ERPBC. Furthermore, increased expression of ADORA1 in ERPBC is associated with a poor outcome. Our observations underscore the context-dependent role of miR-17–92 in breast cancer subtypes and suggest that miR-17–92 could serve as novel prognostic markers in breast cancer.http://www.sciencedirect.com/science/article/pii/S2468294220300599Mir-17–92Adora1Triple negative breast cancerEr-positive breast cancernon-protein coding RNA |
| spellingShingle | Muhammad Mosaraf Hossain Afrin Sultana David Barua Md Nahidul Islam Ananya Gupta Sanjeev Gupta Differential expression, function and prognostic value of miR-17–92 cluster in ER-positive and triple-negative breast cancer Cancer Treatment and Research Communications Mir-17–92 Adora1 Triple negative breast cancer Er-positive breast cancer non-protein coding RNA |
| title | Differential expression, function and prognostic value of miR-17–92 cluster in ER-positive and triple-negative breast cancer |
| title_full | Differential expression, function and prognostic value of miR-17–92 cluster in ER-positive and triple-negative breast cancer |
| title_fullStr | Differential expression, function and prognostic value of miR-17–92 cluster in ER-positive and triple-negative breast cancer |
| title_full_unstemmed | Differential expression, function and prognostic value of miR-17–92 cluster in ER-positive and triple-negative breast cancer |
| title_short | Differential expression, function and prognostic value of miR-17–92 cluster in ER-positive and triple-negative breast cancer |
| title_sort | differential expression function and prognostic value of mir 17 92 cluster in er positive and triple negative breast cancer |
| topic | Mir-17–92 Adora1 Triple negative breast cancer Er-positive breast cancer non-protein coding RNA |
| url | http://www.sciencedirect.com/science/article/pii/S2468294220300599 |
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