title: Tumour-suppressor microRNAs regulate ovarian cancer cell physical properties and invasive behaviour.
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.
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA clarachan27@gmail.com.|Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Clara K
authors.identifier: 0000-0003-2832-4333
authors.initials: CK
authors.lastname: Chan
authors.affiliation: Department of Biochemistry and Biology, University of Houston, Houston, TX, USA.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA.|Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Kendra
authors.initials: K
authors.lastname: Nyberg
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada.|Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada.
authors.forename: Emilia L
authors.initials: EL
authors.lastname: Lim
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada.|Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Steven J M
authors.initials: SJ
authors.lastname: Jones
authors.affiliation: Bio-Rad Laboratories, The Digital Biology Center, Pleasanton, CA, USA.
authors.forename: Dianna
authors.initials: D
authors.lastname: Maar
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada.
authors.forename: Ewan A
authors.initials: EA
authors.lastname: Gibb
authors.affiliation: Department of Biochemistry and Biology, University of Houston, Houston, TX, USA.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Preethi H
authors.initials: PH
authors.lastname: Gunaratne
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada.
authors.forename: A Gordon
authors.initials: AG
authors.lastname: Robertson
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA rowat@ucla.edu.|Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Rowat
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs
keywords: actin cytoskeleton; cell deformability; microfiltration; microfluidics; tumour cell invasion