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MiR-221 is specifically elevated in PC3 cells and its deletion reduces adhesion, motility and growth

Dart, D. Alwyn, Koushyar, Sarah, Lanning, Ben.E and Jiang, Wenguo 2019. MiR-221 is specifically elevated in PC3 cells and its deletion reduces adhesion, motility and growth. Anticancer Research 39 (10) , pp. 5311-5327. 10.21873/anticanres.13724

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Background/Aim: MiR-221, often described both as an oncogenic microRNA and as a tumour suppressor, targets mRNAs involved in carcinogenesis. While other oncogenic microRNAs showed correlations with prostate cancer cell lines' aggressiveness, miR-221 showed an unusual overexpression in PC3. Materials and Methods: CRISPR was used to delete miR-221 from PC3 cells. Analysing the characteristics of PC3miR-221del cells, a reduced growth rate and expression of cell-cycle genes was observed. In global gene expression/ontology analysis of PC3miR-221del cells, cell-cell and cell-substrate adhesion pathways were found to be greatly affected. In addition, reduced levels of adhesion, invasion and motility for PC3miR-221del cells, a change in F-actin localisation and a reduction of EMT markers were observed. Results: The tumour suppressor gene, DIRAS3, was a predicted target of miR-221. In PC3miR-221del cells DIRAS3 was up-regulated at the gene and protein level. Ectopic expression of DIRAS3 in PC3wt cells recapitulated the cellular morphology changes seen in PC3miR-221del cells. DIRAS3 3’UTR was more stable in PC3miR-221del cells, as measured by semi-quantitative PCR and luciferase fusion reporter assays. Conclusion: MiR-221 promotes aggressiveness of PC3 cells by down-regulating DIRAS3, and promoting epithelial-to-mesenchymal transition.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: International Institute of Anticancer Research (IIAR)
ISSN: 0250-7005
Funders: Cardiff China Medical Scholarship
Date of First Compliant Deposit: 2 October 2019
Date of Acceptance: 18 July 2019
Last Modified: 01 Feb 2020 03:18

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