miR-423 Promotes Breast Cancer Invasion by Activating NF-κB Signaling.
NF-κB signaling pathway
TNIP2
breast cancer
miR-423
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2020
2020
Historique:
received:
29
10
2019
accepted:
19
04
2020
entrez:
2
7
2020
pubmed:
2
7
2020
medline:
2
7
2020
Statut:
epublish
Résumé
Breast cancer has become the most common malignancy among women worldwide; therefore, novel diagnostic and prognostic markers and therapeutic targets are urgently required. NF-κB signaling plays a pivotal role in enhancing breast cancer malignant phenotypes, especially cancer invasion and metastasis, which is the main cause of death in cancer patients. TNIP2, an important inhibitor of the NF-κB pathway, is known to involve a negative feedback loop of the NF-κB signaling cascade and to regulate tumor aggressiveness in various cancer types. However, the mRNA level of TNIP2 is barely altered in breast cancer; thus, the mechanism that regulates TNIP2 in breast cancer still needs to be elucidated. We analyzed the expression and prognosis of miR-423 in a TCGA BRCA miRNA cohort and in clinical specimens. We detected the invasive capacity through a Matrigel-coated Transwell penetration assay, a three-dimensional (3D) spheroid invasion assay and a wound healing assay. Then, we applied luciferase assays, real-time PCR assays and Western blotting to further study the mechanism. In this study, analysis of the TCGA BRCA miRNA cohort and clinical specimens demonstrated that miR-423 was upregulated in human breast cancers and was positively correlated with clinical stage, poor overall survival and metastasis classification. Moreover, the invasiveness of breast cancer cells was enhanced by ectopic expression of miR-423 and inhibited by miR-423 downregulation. Mechanistically, upregulation of miR-423 led to activation of the NF-κB signaling pathway and elevated expression of snail and twist, while repression of miR-423 inhibited this pathway. Furthermore, the results indicated that TNIP2 is a target gene of miR-423, and suppression of TNIP2 resulted in increased invasiveness in miR-423-silenced cells. Our results suggest that miR-423 is a crucial factor that enhances breast cancer cell invasion through the NF-κB signaling pathway and shed light on miR-423 as a promising prognostic and therapeutic marker for metastatic breast cancer.
Identifiants
pubmed: 32606763
doi: 10.2147/OTT.S236514
pii: 236514
pmc: PMC7297514
doi:
Types de publication
Journal Article
Langues
eng
Pagination
5467-5478Informations de copyright
© 2020 Dai et al.
Déclaration de conflit d'intérêts
The authors declare that there are no conflicts of interest.
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