MiR-34b/c-5p and the neurokinin-1 receptor regulate breast cancer cell proliferation and apoptosis.
Animals
Apoptosis
/ genetics
Breast Neoplasms
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
Female
Gene Expression Regulation, Neoplastic
/ genetics
Genes, Tumor Suppressor
HEK293 Cells
Humans
MCF-7 Cells
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs
/ biosynthesis
Middle Aged
RNA Interference
RNA, Small Interfering
/ genetics
Receptors, Neurokinin-1
/ agonists
Substance P
/ pharmacology
Xenograft Model Antitumor Assays
Substance P
aprepitant
cell apoptosis
cell proliferation
miR-34
neurokinin-1 receptor
Journal
Cell proliferation
ISSN: 1365-2184
Titre abrégé: Cell Prolif
Pays: England
ID NLM: 9105195
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
16
03
2018
revised:
20
06
2018
accepted:
22
06
2018
pubmed:
20
10
2018
medline:
9
2
2019
entrez:
19
10
2018
Statut:
ppublish
Résumé
MiR-34 is a tumour suppressor in breast cancer. Neurokinin-1 receptor (NK1R), which is the predicted target of the miR-34 family, is overexpressed in many cancers. This study investigated the correlation and clinical significance of miR-34 and NK1R in breast cancer. Western blotting, quantitative reverse transcription-PCR (qRT-PCR) and luciferase assays were conducted to analyse the regulation of NK1R by miR-34 in MDA-MB-231, MCF-7, T47D, SK-BR-3 and HEK-293 T cells. MiR-34b/c-5p, full-length NK1R (NK1R-FL) and truncated NK1R (NK1R-Tr) expression in fifty patients were quantified by qRT-PCR and correlated with their clinicopathological parameters. CCK-8 assays, colony formation assays and flow cytometry were used to measure cell proliferation and apoptosis in MDA-MB-231 and MCF-7 cells transfected with miR-34b/c-5p or NK1R-siRNA and before treatment with or without Substance P (SP), an endogenous peptide agonists of NK1R. The effect of NK1R antagonist aprepitant was also investigated. In vivo xenograft models were used to further verify the regulation of NK1R by miR-34b/c-5p. Expression levels of miR-34b/c-5p and NK1R-Tr, but not NK1R-FL, were associated with enhanced malignant potential, such as tumour stage and Ki67 expression. The overexpression of miR-34b/c-5p or NK1R silencing potently suppressed cell proliferation and induced G2/M phase arrest and the apoptosis of MDA-MB-231 and MCF-7 cells. The NK1R antagonist aprepitant had similar effects. In vivo studies confirmed that miR-34b/c-5p overexpression or NK1R silencing reduced the tumorigenicity of breast cancer. In addition, SP rescued the effects of miR-34b/c-5p overexpression or NK1R silencing on cell proliferation and apoptosis in vitro and in vivo assays. MiR-34b/c-5p and NK1R contribute to breast cancer cell proliferation and apoptosis and are potential targets for breast cancer therapeutics.
Identifiants
pubmed: 30334298
doi: 10.1111/cpr.12527
pmc: PMC6430481
doi:
Substances chimiques
MIRN34 microRNA, human
0
MicroRNAs
0
RNA, Small Interfering
0
Receptors, Neurokinin-1
0
Substance P
33507-63-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12527Subventions
Organisme : Natural Science Foundation of Tianjin City
ID : 16JCYBJC26000
Organisme : National Natural Science Foundation of China
ID : 81201653
Organisme : National Natural Science Foundation of China
ID : 81502519
Informations de copyright
© 2018 The Authors Cell Proliferation Published by John Wiley & Sons Ltd.
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