HMGB1 regulates SNAI1 during NSCLC metastasis, both directly, through transcriptional activation, and indirectly, in a RSF1‐IT2‐dependent manner

Autor: Tao Li, Hai‐bei Dong, Wei Wang, Wen‐wen Guo, Gao‐lei Ma, Yuan‐yuan Chen, Min Xie, Dong-Sheng Pei, Xiao‐jin Wu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
SNAI1
Lung Neoplasms
NSCLC
Metastasis
0302 clinical medicine
Cell Movement
Carcinoma
Non-Small-Cell Lung
HMGB1 Protein
Neoplasm Metastasis
Research Articles
HMGB1
Mice
Inbred BALB C
General Medicine
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Up-Regulation
Gene Expression Regulation
Neoplastic
Oncology
030220 oncology & carcinogenesis
Molecular Medicine
Regression Analysis
miR‐129‐5p
Female
RNA
Long Noncoding
RSF1‐IT2
Research Article
Transcriptional Activation
Down-Regulation
Mice
Nude
chemical and pharmacologic phenomena
Biology
Models
Biological
lcsh:RC254-282
03 medical and health sciences
Cell Line
Tumor
Genetics
medicine
Animals
Humans
Neoplasm Invasiveness
Lung cancer
Proportional Hazards Models
Base Sequence
Mechanism (biology)
Competing endogenous RNA
medicine.disease
respiratory tract diseases
MicroRNAs
030104 developmental biology
Tumor progression
biology.protein
Cancer research
Snail Family Transcription Factors
Function (biology)
Zdroj: Molecular Oncology, Vol 14, Iss 6, Pp 1348-1364 (2020)
Molecular Oncology
ISSN: 1574-7891
1878-0261
Popis: 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.
Dual‐mode regulation of SNAI1 by HMGB1 in NSCLC metastasis.
Databáze: OpenAIRE
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