SNHG16/miR-605-3p/TRAF6/NF-κB feedback loop regulates hepatocellular carcinoma metastasis.
Base Sequence
Carcinoma, Hepatocellular
/ genetics
Cell Line, Tumor
Cell Survival
/ genetics
Disease-Free Survival
Down-Regulation
/ genetics
Epithelial-Mesenchymal Transition
/ genetics
Feedback, Physiological
Female
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms
/ genetics
Male
MicroRNAs
/ genetics
Middle Aged
Multivariate Analysis
NF-kappa B
/ metabolism
Neoplasm Metastasis
Prognosis
RNA, Long Noncoding
/ genetics
TNF Receptor-Associated Factor 6
/ metabolism
miR-605-3p
NF-κB signalling
feedback loop
hepatocellular carcinoma
metastasis
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
07
11
2019
revised:
30
03
2020
accepted:
27
04
2020
pubmed:
22
5
2020
medline:
29
4
2021
entrez:
22
5
2020
Statut:
ppublish
Résumé
The mechanism by which miR-605-3p regulates hepatocellular carcinoma (HCC) metastasis has not been clarified. In this study, we found that miR-605-3p was down-regulated in HCC and that low miR-605-3p expression was associated with tumour thrombus and tumour satellites. HCC patients with low miR-605-3p expression showed shorter overall survival and disease-free survival after surgery. Overexpression of miR-605-3p inhibited epithelial-mesenchymal transition and metastasis of HCC through NF-κB signalling by directly inhibiting expression of TRAF6, while silencing of miR-605-3p had the opposite effect. We also found that SNHG16 directly bound to miR-605-3p as a competing endogenous RNA. Mechanistically, high expression of SNHG16 promoted binding to miR-605-3p and inhibited its activity, which led to up-regulation of TRAF6 and sustained activation of the NF-κB pathway, which in turn promoted epithelial-mesenchymal transition and metastasis of HCC. TRAF6 increased SNHG16 promoter activity by activating NF-κB, thereby promoting the transcriptional expression of SNHG16 and forming a positive feedback loop that aggravated HCC malignancy. Our findings reveal a mechanism for the sustained activation of the SNHG16/miR-605-3p/TRAF6/NF-κB feedback loop in HCC and provide a potential target for a new HCC treatment strategy.
Identifiants
pubmed: 32436333
doi: 10.1111/jcmm.15399
pmc: PMC7339162
doi:
Substances chimiques
MIRN605 microRNA, human
0
MicroRNAs
0
NF-kappa B
0
RNA, Long Noncoding
0
SNHG16 lncRNA, human
0
TNF Receptor-Associated Factor 6
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7637-7651Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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