Abstract 1980MO
Background
SUMO specific peptidase 1(SENP1) is an important factor involved in the regulation of small ubiquitin-related modifier (SUMO) modification. Our previous research has shown that SENP1 could be a potential tumour-promoting factor in non-small cell lung cancer (NSCLC). However, its role in tumour progression remains largely unknown. This study aims to characterize the role of SENP1 in lung adenocarcinoma.
Methods
The TCGA database provided us expression profiles of SENP1 and overall survival rates. loss-of-function assays were performed to examine the effect of SENP1 on proliferation, migration and invasion of lung adenocarcinoma cells in vitro and in vivo. Immunoprecipitation (IP), western blot and quantitative real time PCR (qRT-PCR) were carried out to reveal the interrelation between SENP1, SIRT6 and AAT (amino acid transporter) genes signal pathway.
Results
In this study, we found that SENP1 was expressed at high levels in lung adenocarcinoma tissues and advanced TNM stages and was significantly associated with poor prognosis. we also found that SENP1 knockdown inhibited lung adenocarcinoma cell progression in vitro and in vivo. SUMOylation of SIRT6 was also observed in lung adenocarcinoma, and it was reduced by SENP1. SUMOylation of SIRT6 specifically increased its deacetylation of histone H3 on lysine 56 instead of that of lysine 9 (H3K9) in an in vitro model. Mechanistically, we found that knockdown of SENP1 reduced the expression of AAT genes by decreasing H3K56 acetylation through increasing SIRT6 SUMOylation. Moreover, mutation of the SUMOylation sites of Sirt6 reduced its tumour-suppressive effects.
Conclusions
These results revealed that SENP1 promotion of tumour progression in lung adenocarcinoma and its tumour-promoting effects might be attributed to its important role in the regulation of Sirt6 SUMOylation and the expression of AAT genes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The National Natural Science Foundation of China the Beijing Municipal Natural Science Foundation.
Disclosure
All authors have declared no conflicts of interest.
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