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| Status |
Public on Feb 23, 2022 |
| Title |
Loss of REST in breast cancer promotes tumor progression through estrogen sensitization, MMP24 and CEMIP overexpression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Loss of REST function is seen in ~20% of breast cancers and is associated with a more aggressive phenotype and poor prognosis. Despite the frequent loss of REST, little is known about the role of REST in the molecular pathogenesis of breast cancer. We then utilized gene knockdown in MCF-7 cells in the presence or absence of steroid hormones estrogen and/ progesterone followed by RNA sequencing in an attempt to understand the tumor suppressor role of REST in breast cancer. We show that REST directly regulates CEMIP (cell migration-inducing and hyaluronan-binding protein, KIAA1199) and MMP24 (matrix metallopeptidase 24), genes known to have roles in invasion and metastasis. REST knockdown in breast cancer cells leads to significant upregulation of CEMIP and MMP24. In addition, we found REST binds to RE-1 sites (repressor element-1) within the genes and influences their transcription. Furthermore, we found that the estrogen receptor (ESR1) signaling pathway is activated in the absence of REST, regardless of hormone treatment. We demonstrate a critical role for the loss of REST in aggressive breast cancer pathogenesis and provide evidence for REST as an important diagnostic marker for personalized treatment plans.
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| Overall design |
mRNA profiles of MCF-7 cells treated with vehicle, estrogen, progesterone, or both in the presence of siControl or siREST transfections. Duplicates of each sample were included.
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| Contributor(s) |
Cloud AS, Vargheese AM, Gunewardena S, Shimak RM, Ganeshkumar S, Kumaraswamy E, Jensen RA, Chennathukuzhi VM |
| Citation(s) |
35177031 |
| Submission date |
May 04, 2021 |
| Last update date |
Feb 23, 2022 |
| Contact name |
Sumedha S Gunewardena |
| Phone |
9139456878
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| Organization name |
University of kansas medical center
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| Department |
Dept. of Molecular and Integrative Physiology
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| Street address |
2146 West 39th Avenue
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| City |
Kansas City |
| State/province |
Kansas |
| ZIP/Postal code |
66160 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA727316 |
| SRA |
SRP318455 |
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