Targeting of CCBE1 by miR-330-3p in human breast cancer promotes metastasis
Identifieur interne : 000133 ( Main/Exploration ); précédent : 000132; suivant : 000134Targeting of CCBE1 by miR-330-3p in human breast cancer promotes metastasis
Auteurs : Aruz Mesci [Canada] ; Xiaoyong Huang [Canada] ; Samira Taeb [Canada] ; Sahar Jahangiri [Canada] ; Yohan Kim [Canada] ; Emmanouil Fokas [Royaume-Uni] ; Jeff Bruce [Canada] ; Hon S. Leong [Canada] ; Stanley K. Liu [Canada]Source :
- British Journal of Cancer [ 0007-0920 ] ; 2017.
Abstract
MicroRNAs (miRs) are involved in the regulation of many processes that contribute to malignancy, including cell proliferation, radiation resistance, invasion and metastasis. The role of miR-330-3p, an miR upregulated in breast cancer, remains unclear.
We examine the association of miR-330-3p with distant relapse-free survival in the Oxford cohort of breast cancer patients. We also study miR-330-3p function using
miR-330-3p is enriched in breast cancer, and higher levels of miR-330-3p expression are associated with lower distant relapse-free survival in a cohort of breast cancer patients. Consistent with these observations, overexpression of miR-330-3p in breast cancer cell lines results in greater invasiveness
We show for the first time that miR-330-3p targets CCBE1 to promote invasion and metastasis. miR-330-3p and CCBE1 may represent promising biomarkers in breast cancer.
Url:
DOI: 10.1038/bjc.2017.105
PubMed: 28419078
PubMed Central: 5482727
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><sec><title>Background:</title>
<p>MicroRNAs (miRs) are involved in the regulation of many processes that contribute to malignancy, including cell proliferation, radiation resistance, invasion and metastasis. The role of miR-330-3p, an miR upregulated in breast cancer, remains unclear.</p>
</sec>
<sec><title>Methods:</title>
<p>We examine the association of miR-330-3p with distant relapse-free survival in the Oxford cohort of breast cancer patients. We also study miR-330-3p function using <italic>in vitro</italic>
invasion and <italic>ex ovo</italic>
metastasis assays. Using <italic>in vitro</italic>
luciferase assays, we validate a novel target gene for miR-330-3p, Collagen And Calcium Binding EGF Domains 1 (CCBE1). We assess functional consequences of CCBE1 loss by using siRNA-mediated knockdown followed by <italic>in vitro</italic>
invasion assays. Lastly, we examine the expression profile of CCBE1 in breast carcinomas in the Curtis and TCGA Breast Cancer data sets using Oncomine Platform as well as distant relapse-free and overall survival of patients in the Helsinki University breast cancer data set according to CCBE1 expression status.</p>
</sec>
<sec><title>Results:</title>
<p>miR-330-3p is enriched in breast cancer, and higher levels of miR-330-3p expression are associated with lower distant relapse-free survival in a cohort of breast cancer patients. Consistent with these observations, overexpression of miR-330-3p in breast cancer cell lines results in greater invasiveness <italic>in vitro</italic>
, and miR-330-3p-overexpressing cells also metastasise more aggressively <italic>ex ovo</italic>
. We identify CCBE1 as a direct target of miR-330-3p, and show that knockdown of CCBE1 results in a greater invasive capacity. Accordingly, in breast cancer patients CCBE1 is frequently downregulated, and its loss is associated with reduced distant relapse-free and overall survival.</p>
</sec>
<sec><title>Conclusions:</title>
<p>We show for the first time that miR-330-3p targets CCBE1 to promote invasion and metastasis. miR-330-3p and CCBE1 may represent promising biomarkers in breast cancer.</p>
</sec>
</div>
</front>
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