An integrated analysis to predict micro-RNAs targeting both stemness and metastasis in breast cancer stem cells

Rahimi, M ; Sharif University of Technology | 2019

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  1. Type of Document: Article
  2. DOI: 10.1111/jcmm.14090
  3. Publisher: Blackwell Publishing Inc , 2019
  4. Abstract:
  5. Several evidences support the idea that a small population of tumour cells representing self-renewal potential are involved in initiation, maintenance, metastasis, and outcomes of cancer therapy. Elucidation of microRNAs/genes regulatory networks activated in cancer stem cells (CSCs) is necessary for the identification of new targets for cancer therapy. The aim of the present study was to predict the miRNAs pattern, which can target both metastasis and self-renewal pathways using integration of literature and data mining. For this purpose, mammospheres derived from MCF-7, MDA-MB231, and MDA-MB468 were used as breast CSCs model. They had higher migration, invasion, and colony formation potential, with increasing in stemness- and EMT-related genes expression. Our results determined that miR-204, -200c, -34a, and -10b contemporarily could target both self-renewal and EMT pathways. This core regulatory of miRNAs could increase the survival rate of breast invasive carcinoma via up-regulation of OCT4, SOX2, KLF4, c-MYC, NOTCH1, SNAI1, ZEB1, and CDH2 and down-regulation of CDH1. The majority of those target genes were involved in the regulation of pluripotency, MAPK, WNT, Hedgehog, p53, and transforming growth factor β pathways. Hence, this study provides novel insights for targeting core regulatory of miRNAs in breast CSCs to target both self-renewal and metastasis potential and eradication of breast cancer
  6. Keywords:
  7. Breast cancer stem cell ; EMT ; Metastasis ; MiRNAs ; Self-renewal ; Basic fibroblast growth factor receptor ; DNA (cytosine 5) methyltransferase 1 ; Epidermal growth factor ; Fas ligand ; Interleukin 6 ; kruppel like factor 4 ; MicroRNA ; MicroRNA 10b 5p ; MicroRNA 200c ; MicroRNA 200c 3p ; MicroRNA 204 5p ; MicroRNA 21 5p ; MicroRNA 30c 5p ; MicroRNA 34a 5p ; MicroRNA 373 3p ; MicroRNA 520c 3p ; Mitogen activated protein kinase 1 ; Notch1 receptor ; Octamer transcription factor 4 ; Protein p53 ; Smad4 protein ; Sonic hedgehog protein ; Transcription factor Elk 1 ; Transcription factor Gli1 ; Transcription factor Sox2 ; Transcription factor ZEB1 ; Transforming growth factor beta ; Twist related protein 1 ; unclassified drug ; unindexed drug ; Wnt protein ; Bioinformatics ; Biology ; Breast cancer ; Cancer stem cell ; Cancer therapy ; Cell invasion assay ; Cell migration assay ; Colony formation ; Controlled study ; Qene expression ; Qene ontology ; Qenotype phenotype correlation ; Human ; Human cell ; Integrated health care system ; MCF-7 cell line ; MDA-MB-231 cell line ; MDA-MB-468 cell line ; Molecular biology ; Monolayer culture ; Priority journal ; Prognostic assessment ; Real time polymerase chain reaction ; Receptor down regulation ; Receptor upregulation ; RNA isolation ; Signal transduction ; Survival analysis ; Survival rate ; Tissue culture ; Validation process
  8. Source: Journal of Cellular and Molecular Medicine ; Volume 23, Issue 4 , 2019 , Pages 2442-2456 ; 15821838 (ISSN)
  9. URL: https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.14090