HMGB1 regulates SNAI1 during NSCLC metastasis, both directly, through transcriptional activation, and indirectly, in a RSF1-IT2-dependent manner.
Animals
Base Sequence
Carcinoma, Non-Small-Cell Lung
/ genetics
Cell Line, Tumor
Cell Movement
/ genetics
Down-Regulation
/ genetics
Female
Gene Expression Regulation, Neoplastic
HMGB1 Protein
/ metabolism
Humans
Lung Neoplasms
/ genetics
Mice, Inbred BALB C
Mice, Nude
MicroRNAs
/ genetics
Models, Biological
Neoplasm Invasiveness
Neoplasm Metastasis
Prognosis
Proportional Hazards Models
RNA, Long Noncoding
/ genetics
Regression Analysis
Snail Family Transcription Factors
/ genetics
Transcriptional Activation
/ genetics
Up-Regulation
/ genetics
HMGB1
NSCLC
RSF1-IT2
SNAI1
miR-129-5p
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
20
09
2019
revised:
16
01
2020
accepted:
15
04
2020
pubmed:
20
4
2020
medline:
1
7
2021
entrez:
20
4
2020
Statut:
ppublish
Résumé
High-mobility group protein B1 (HMGB1) has important functions in cancer cell proliferation and metastasis. However, the mechanisms of HMGB1 function in non-small-cell lung cancer (NSCLC) remain unclear. This study aimed to investigate the underlying mechanism of HMGB1-dependent tumor cell proliferation and NSCLC metastasis. Firstly, we found high HMGB1 expression in NSCLC and showed that HMBG1 promoted proliferation, migration, and invasion of NSCLC cells. HMGB1 could bind to SNAI1 promoter and activate the expression of SNAI1. In addition, HMGB1 could transcriptionally regulate the lncRNA RSF1-IT2. RSF1-IT2 was found to function as ceRNA, sponging miR-129-5p, which targets SNAI1. Notably, HMGB1 was also identified as a target of miR-129-5p, which indicates the establishment of a positive feedback loop. Consequently, high expression of RSF1-IT2 and SNAI1 was found to closely correlate with tumor progression in both HMGB1-overexpressing xenograft nude mice and patients with NSCLC. Taken together, our findings provide new insights into molecular mechanisms of HMGB1-dependent tumor metastasis. Components of the HMGB1-RSF1-IT2-miR-129-5p-SNAI1 pathway may have a potential as prognostic and therapeutic targets in NSCLC.
Identifiants
pubmed: 32306523
doi: 10.1002/1878-0261.12691
pmc: PMC7266277
doi:
Substances chimiques
HMGB1 Protein
0
MicroRNAs
0
Mirn129 microRNA, human
0
RNA, Long Noncoding
0
SNAI1 protein, human
0
Snail Family Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1348-1364Informations de copyright
© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
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