Title | Tumour-suppressor microRNAs regulate ovarian cancer cell physical properties and invasive behaviour. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Chan, CK, Pan, Y, Nyberg, K, Marra, MA, Lim, EL, Jones, SJM, Maar, D, Gibb, EA, Gunaratne, PH, A Robertson, G, Rowat, AC |
Journal | Open Biol |
Volume | 6 |
Issue | 11 |
Date Published | 2016 Nov |
ISSN | 2046-2441 |
Keywords | Actin Cytoskeleton, Cell Line, Tumor, Cell Movement, Female, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, MicroRNAs, Neoplasm Invasiveness, Ovarian Neoplasms, Signal Transduction, Up-Regulation |
Abstract | The activities of pathways that regulate malignant transformation can be influenced by microRNAs (miRs). Recently, we showed that increased expression of five tumour-suppressor miRs, miR-508-3p, miR-508-5p, miR-509-3p, miR-509-5p and miR-130b-3p, correlate with improved clinical outcomes in human ovarian cancer patients, and that miR-509-3p attenuates invasion of ovarian cancer cell lines. Here, we investigate the mechanism underlying this reduced invasive potential by assessing the impact of these five miRs on the physical properties of cells. Human ovarian cancer cells (HEYA8, OVCAR8) that are transfected with miR mimics representing these five miRs exhibit decreased invasion through collagen matrices, increased cell size and reduced deformability as measured by microfiltration and microfluidic assays. To understand the molecular basis of altered invasion and deformability induced by these miRs, we use predicted and validated mRNA targets that encode structural and signalling proteins that regulate cell mechanical properties. Combined with analysis of gene transcripts by real-time PCR and image analysis of F-actin in single cells, our results suggest that these tumour-suppressor miRs may alter cell physical properties by regulating the actin cytoskeleton. Our findings provide biophysical insights into how tumour-suppressor miRs can regulate the invasive behaviour of ovarian cancer cells, and identify potential therapeutic targets that may be implicated in ovarian cancer progression. |
DOI | 10.1098/rsob.160275 |
Alternate Journal | Open Biol |
PubMed ID | 27906134 |
PubMed Central ID | PMC5133448 |
Grant List | P30 AI028697 / AI / NIAID NIH HHS / United States P30 CA016042 / CA / NCI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States |
Tumour-suppressor microRNAs regulate ovarian cancer cell physical properties and invasive behaviour.
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