YBX1 gene silencing inhibits migratory and invasive potential via CORO1C in breast cancer in vitro

Abstract

BackgroundY-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.MethodsSilencing 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.ResultsDownregulation 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.ConclusionIt 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3187-7) contains supplementary material, which is available to authorized users.

Differential Proteomic Analysis between Small Cell Lung Carcinoma (SCLC) and Pulmonary Carcinoid Tumors Reveals Molecular Signatures for Malignancy in Lung Cancer

“…Interactions among CORO1C, RCC2, and RAC1 guide mesenchymal migration through RAC1 trafficking. In a breast cancer cell line, transient overexpression of CORO1C resulted in increased cell migration and invasion, which was abrogated by knockdown of YBX1, an evolutionary conserved transcription and translation regulating protein that is overexpressed in various human malignancies . We clearly identified that both RCC2 and CORO1C were significantly overexpressed in SCLC.…”

Exploring the RNA landscape of endothelial exosomes

“…Finally, YB1 is a protein involved in DNA repair and replication, and in RNA decay, stability, and transcription (Eliseeva et al 2011;Lyabin et al 2014). It has been mainly studied regarding its role in cancer progression and maintenance (Jung et al 2014;Guo et al 2017;Lim et al 2017). Among other studies, two of special interest are the study published by Zhao et al (2017) where they found that YB1 can interact with the lncRNA AWPPH in hepatocellular carcinoma cells promoting cellular growth; and the study by Wu et al (2015), where they described that YB1 can regulate the expression and maturation of microRNAs via the binding of specific motifs.…”

Identifying a combined biomarker for bisphosphonate‐related osteonecrosis of the jaw

“…They included significant biological pathways, the 10 most significant of which were phosphoprotein, acetylation, protein binding, poly (A) RNA binding, nucleoplasm, isopeptide bond, Ubl conjugation, extracellular exosome, mutagenesis site, and nucleus; the 10 pathways included YBX1 and HNRNPC. YBX1 was once not known to be associated with BRONJ, but then numerous studies reported that it played a role in cancer progression . HNRNPC was also identified as a candidate biomarker for chemoresistance in gastric cancer …”

“…YBX1 was once not known to be associated with BRONJ, but then numerous studies reported that it played a role in cancer progression. [39][40][41][42] HNRNPC was also identified as a candidate biomarker for chemoresistance in gastric cancer. 43 There are 2 potential approaches to analyzing gene expression data in microarray studies.…”