Please use this identifier to cite or link to this item: https://doi.org/10.1186/s12885-017-3187-7
Title: YBX1 gene silencing inhibits migratory and invasive potential via CORO1C in breast cancer in vitro
Authors: Lim, J.P
Shyamasundar, S
Gunaratne, J 
Scully, O.J
Matsumoto, K
Bay, B.H 
Keywords: small interfering RNA
Y box binding protein 1
actin binding protein
coronin proteins
Y box binding protein 1
YBX1 protein, human
Article
breast cancer
breast cancer cell line
cell culture
cell invasion
cell migration
controlled study
CORO1C gene
distant metastasis
DNA microarray
gene
gene overexpression
gene silencing
genetic regulation
human
human cell
in vitro study
luciferase assay
real time polymerase chain reaction
receptor down regulation
transcriptomics
YBX1 gene
breast tumor
cell motion
cell proliferation
female
gene expression regulation
genetics
pathology
tumor cell line
tumor invasion
Breast Neoplasms
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Humans
Microfilament Proteins
Neoplasm Invasiveness
Y-Box-Binding Protein 1
Issue Date: 2017
Publisher: BioMed Central Ltd.
Citation: Lim, J.P, Shyamasundar, S, Gunaratne, J, Scully, O.J, Matsumoto, K, Bay, B.H (2017). YBX1 gene silencing inhibits migratory and invasive potential via CORO1C in breast cancer in vitro. BMC Cancer 17 (1) : 201. ScholarBank@NUS Repository. https://doi.org/10.1186/s12885-017-3187-7
Abstract: Background: Y-box binding protein-1 is an evolutionary conserved transcription and translation regulating protein that is overexpressed in various human malignancies, including breast cancer. Despite reports of YB-1 and its association with distant spread of breast cancer, the intrinsic mechanism underlying this observation remains elusive. This study investigates the role of YB-1 in mediating metastasis in highly invasive breast cancer cell lines. Methods: Silencing the YBX1 gene (which encodes the YB-1 protein) by small interfering RNA (siRNA) was performed in MDA-MB-231 and Hs578T breast cancer cell lines, followed by phenotypic assays including cell migration and invasion assays. Gene expression profiling using Affymetrix GeneChip® Human Transcriptome 2.0 array was subsequently carried out in YB-1 silenced MDA-MB-231 cells. Overexpression and silencing of YBX1 were performed to assess the expression of CORO1C, one of the differentially regulated genes from the transcriptomic analysis. A Gaussia luciferase reporter assay was used to determine if CORO1C is a putative YB-1 downstream target. siRNA-mediated silencing of CORO1C and down-regulation of YBX1 in CORO1C overexpressing MDA-MB-231 cells were performed to evaluate cell migration and invasion. Results: Downregulation of the YB-1 protein inhibited cell migration and invasion in MDA-MB-231 breast cancer cells. Global gene expression profiling in the YBX1 silenced MDA-MB-231 cells identified differential expression of several genes, including CORO1C (which encodes for an actin binding protein, coronin-1C) as a potential downstream target of YB-1. While knockdown of YBX1 gene decreased CORO1C gene expression, the opposite effects were seen in YB-1 overexpressing cells. Subsequent verification using the reporter assay revealed that CORO1C is an indirect downstream target of YB-1. Silencing of CORO1C by siRNA in MDA-MB-231 cells was also observed to reduce cell migration and invasion. Silencing of YBX1 caused a similar reduction in CORO1C expression, concomitant with a significant decrease in migration in Hs578T cells. In coronin-1C overexpressing MDA-MB-231 cells, increased migration and invasion were abrogated by YB-1 knockdown. Conclusion: It would appear that YB-1 could regulate cell invasion and migration via downregulation of its indirect target coronin-1C. The association between YB-1 and coronin-1C offers a novel approach by which metastasis of breast cancer cells could be targeted and abrogated. © 2017 The Author(s).
Source Title: BMC Cancer
URI: https://scholarbank.nus.edu.sg/handle/10635/173854
ISSN: 14712407
DOI: 10.1186/s12885-017-3187-7
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