Overexpression of miR-361-5p in triple-negative breast cancer (TNBC) inhibits migration and invasion by targeting RQCD1 and inhibiting the EGFR/PI3K/Akt pathway.
Adult
Breast Neoplasms
/ metabolism
Cell Line, Tumor
Cell Movement
/ genetics
ErbB Receptors
/ biosynthesis
Female
Humans
MicroRNAs
/ biosynthesis
Neoplasm Invasiveness
/ genetics
Oncogene Protein v-akt
/ biosynthesis
Phosphatidylinositol 3-Kinases
/ biosynthesis
Phosphorylation
/ genetics
Signal Transduction
/ genetics
Transcription Factors
/ biosynthesis
Triple Negative Breast Neoplasms
/ metabolism
Journal
Bosnian journal of basic medical sciences
ISSN: 1840-4812
Titre abrégé: Bosn J Basic Med Sci
Pays: Bosnia and Herzegovina
ID NLM: 101200947
Informations de publication
Date de publication:
12 Feb 2019
12 Feb 2019
Historique:
received:
23
03
2018
accepted:
15
05
2018
pubmed:
21
6
2018
medline:
14
6
2019
entrez:
21
6
2018
Statut:
epublish
Résumé
Triple-negative breast cancer (TNBC) is the leading cause of cancer-related death in women. Previous studies indicated that miR-361-5p was downregulated in breast cancer, however, the exact effect of miR-361-5p on TNBC requires further investigation. In the present study, we investigated whether miR-361-5p can act as a tumor suppressor by targeting required for cell differentiation 1 homolog (RQCD1) and inhibiting epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway in TNBC. The expression of miR-361-5p and RQCD1 was determined by quantitative reverse transcription PCR (qRT-PCR) and/or western blot in TNBC and the adjacent tissues. miR-361-5p mimics were constructed and transfected to TNBC cell line MDA-MB-231. Cells were divided into three groups: blank control group, miRNA mimic negative control (NC) group, and miR-361-5p mimics group. Expression of miR-361-5p, mRNA and protein expression of PI3K, Akt, EGFR, phosphorylated (p)-EGFR/PI3K/Akt, and protein expression of RQCD1 and matrix metallopeptidase 9 (MMP-9) in MDA-MB-231 were measured by qRT-PCR/western blot after transfection. Cell viability was determined by CCK-8 assay. Cell migration and invasion ability were evaluated by scratch and transwell assay, respectively. miR-361-5p target gene was determined by bioinformatics analysis and luciferase reporter assay. RQCD1 was identified as a target of miR-361-5p by TargetScan and confirmed by luciferase reporter assay. Downregulated miR-361-5p and upregulated RQCD1 were observed in TNBC tissues. Expression of EGFR, PI3K, Akt and MMP-9 was inhibited in cells treated with miR-361-5p mimics. Transfection of miR-361-5p mimics also inhibited the phosphorylation of EGFR, PI3K, and Akt. Suppressed cell viability, migration, and invasion was found in miR-361-5p mimics groups. Our results indicated that overexpression of miR-361-5p might act as a suppressor in TNBC by targeting RQCD1 to inhibit the EGFR/PI3K/Akt signaling pathway.
Identifiants
pubmed: 29924958
doi: 10.17305/bjbms.2018.3399
pmc: PMC6387672
doi:
Substances chimiques
CNOT9 protein, human
0
MIRN361 microRNA, human
0
MicroRNAs
0
Transcription Factors
0
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Oncogene Protein v-akt
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
52-59Références
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