A1 Journal article – refereed
Excess of a Rassf1-targeting microRNA, miR-193a-3p, perturbs cell division fidelity




List of Authors: Sofia Pruikkonen, Marko J Kallio
Publisher: NATURE PUBLISHING GROUP
Place: United Kingdom
Publication year: 2017
Journal: British Journal of Cancer
Journal name in source: BRITISH JOURNAL OF CANCER
Journal acronym: BRIT J CANCER
Volume number: 116
Number of pages: 11
ISSN: 0007-0920
eISSN: 1532-1827

Abstract
Background: Several microRNA (miRNA) molecules have emerged as important post-transcriptional regulators of tumour suppressor and oncogene expression. Ras association domain family member 1 (RASSF1) is a critical tumour suppressor that controls multiple aspects of cell proliferation such as cell cycle, cell division and apoptosis. The expression of RASSF1 is lost in a variety of cancers due to the promoter hypermethylation.Methods: miR-193a-3p was identified as a RASSF1-targeting miRNA by a dual screening approach. In cultured human cancer cells, immunoblotting, qRT-PCR, luciferase reporter assays, time-lapse microscopy and immunofluorescence methods were used to study the effects of excess miR-193a-3p on RASSF1 expression and cell division.Results: Here, we report a new miRNA-mediated mechanism that regulates RASSF1 expression: miR-193a-3p binds directly to RASSF1-30UTR and represses the mRNA and protein expression. In human cancer cells, excess of miR-193a-3p causes polyploidy through impairment of the Rassf1-Syntaxin 16 signalling pathway that is needed for completion of cytokinesis. In the next cell cycle the miR-193a-3p-overexpressing cells exhibit multipolar mitotic spindles, mitotic delay and elevated frequency of cell death.Conclusions: Our results suggest that besides epigenetic regulation, altered expression of specific miRNAs may contribute to the loss of Rassf1 in cancer cells and cause cell division errors.

Last updated on 2019-20-07 at 07:37