miR-622 is a novel potential biomarker of breast carcinoma and impairs motility of breast cancer cells through targeting NUAK1 kinase.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
24
07
2019
accepted:
24
04
2020
revised:
03
04
2020
pubmed:
19
5
2020
medline:
26
2
2021
entrez:
19
5
2020
Statut:
ppublish
Résumé
Aberrant expression of microRNAs (miR) has been proposed as non-invasive biomarkers for breast cancers. The aim of this study was to analyse the miR-622 level in the plasma and in tissues of breast cancer patients and to explore the role of miR-622 and its target, the NUAK1 kinase, in this context. miR-622 expression was analysed in plasma and in tissues samples of breast cancer patients by q-RT-PCR. Bioinformatics programs, luciferase assay, public dataset analysis and functional experiments were used to uncover the role of miR-622 and its target in breast cancer cells. miR-622 is downregulated in plasma and in tissues of breast cancer patients respect to healthy controls and its downregulation is significantly associated with advanced grade and high Ki67 level. Modulation of miR-622 affects the motility phenotype of breast cancer cells. NUAK1 kinase is a functional target of miR-622, it is associated with poor clinical outcomes of breast cancer patients and is inversely correlated with miR-622 level. miR-622/NUAK1 axis is deregulated in breast cancer patients and affects the motility phenotype of breast cancer cells. Importantly, miR-622 and NUAK1 hold promises as biomarkers and as targets for breast cancers.
Sections du résumé
BACKGROUND
Aberrant expression of microRNAs (miR) has been proposed as non-invasive biomarkers for breast cancers. The aim of this study was to analyse the miR-622 level in the plasma and in tissues of breast cancer patients and to explore the role of miR-622 and its target, the NUAK1 kinase, in this context.
METHODS
miR-622 expression was analysed in plasma and in tissues samples of breast cancer patients by q-RT-PCR. Bioinformatics programs, luciferase assay, public dataset analysis and functional experiments were used to uncover the role of miR-622 and its target in breast cancer cells.
RESULTS
miR-622 is downregulated in plasma and in tissues of breast cancer patients respect to healthy controls and its downregulation is significantly associated with advanced grade and high Ki67 level. Modulation of miR-622 affects the motility phenotype of breast cancer cells. NUAK1 kinase is a functional target of miR-622, it is associated with poor clinical outcomes of breast cancer patients and is inversely correlated with miR-622 level.
CONCLUSIONS
miR-622/NUAK1 axis is deregulated in breast cancer patients and affects the motility phenotype of breast cancer cells. Importantly, miR-622 and NUAK1 hold promises as biomarkers and as targets for breast cancers.
Identifiants
pubmed: 32418991
doi: 10.1038/s41416-020-0884-9
pii: 10.1038/s41416-020-0884-9
pmc: PMC7403386
doi:
Substances chimiques
3' Untranslated Regions
0
Biomarkers, Tumor
0
MIRN622 microRNA, human
0
MicroRNAs
0
Repressor Proteins
0
Protein Kinases
EC 2.7.-
NUAK1 protein, human
EC 2.7.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
426-437Subventions
Organisme : Ministero della Salute (Ministry of Health, Italy)
ID : Ricerca Corrente
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)
ID : Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN) -Bando 2017- grant 2017MHJJ55
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