Evaluating the role of hsa-miR-200c in reversing the epithelial to mesenchymal transition in prostate cancer
Autor: | Keya Basu, Pramita Chowdhury, Dilip Karmakar, Amrita Chaudhary, Deepmala Karmakar, Sanghamitra Sengupta, Sanmitra Basu, Jyotirmoy Chatterjee |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Epithelial-Mesenchymal Transition Slug Vimentin 03 medical and health sciences Prostate cancer 0302 clinical medicine Cell Movement Cell Line Tumor Genetics medicine Humans Epithelial–mesenchymal transition Transcription factor Cell Proliferation biology Gene Expression Profiling Mesenchymal stem cell Cancer Prostatic Neoplasms Zinc Finger E-box-Binding Homeobox 1 General Medicine medicine.disease biology.organism_classification Gene expression profiling Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis embryonic structures PC-3 Cells Cancer research biology.protein Snail Family Transcription Factors Transcriptome |
Zdroj: | Gene. 730 |
ISSN: | 1879-0038 |
Popis: | Deregulated epithelial-to-mesenchymal transition constitutes one of the major aspects of cancer progression. In this study, to identify key molecular principles of EMT pathway in prostate carcinogenesis, an elaborate gene expression profiling was conducted by qRT-PCR and Western blot analyses. A preponderance of mesenchymal trait was observed in the pathological samples of prostate cancer. To simulate an appropriate in vitro model, PC3 cell line was subjected to hypoxic stress, which resulted in elevated expression of vimentin along with EMT-mediating transcription factors Zeb1 and Slug. To conciliate this mesenchymal behavior of PC3 cells, hsa-miR-200c was deliberately overexpressed which led to a marked reduction of cell motility and expression of vimentin, N-cadherin, Zeb1 and Slug with concurrent increase in level of β-catenin. hsa-miR-200c was demonstrated to appease hypoxia-aggravated changes in cellular morphology by coordinated repression of vimentin, Zeb1 and Slug. Mode of action for hsa-miR-200c was mediated through transcriptional repression of Zeb1 and Slug interacting with E-box sequences in the vimentin promoter as documented by promoter assay. This ability of hsa-miR-200c to reclaim epithelial traits leads to the anticipation that molecular reprogramming of Zeb1-Slug/vimentin axis may relieve aggressiveness of prostate cancer. |
Databáze: | OpenAIRE |
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