Molecular mechanism of NEDD8-conjugating enzyme UBE2F regulat-ing lung adenocarcinoma metastasis
10.12092/j.issn.1009-2501.2024.06.002
- VernacularTitle:NEDD8结合酶UBE2F调控肺腺癌转移的分子机制研究
- Author:
Xiongzhi LIN
1
,
2
;
Luyi ZHANG
;
Lianping HE
;
Yong LIANG
;
Lisha ZHOU
Author Information
1. 河北北方学院研究生学院,张家口 075000,河北
2. 台州学院医学院,台州 318000,浙江
- Keywords:
NEDD8-conjugatingenzyme E2;
UBE2F;
Snail;
lungadenocarcinoma;
metastasis
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2024;29(6):612-620
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To study the effect of NEDD8-conjugating enzyme UBE2F on lung adenocarcino-ma metastasis.METHODS:The expression of UBE2F in lung adenocarcinoma was analyzed using TIMER2.0,UALCAN and HPA databases.Kaplan-Mei-er Plotter database was used to analyze the rela-tionship between UBE2F expression and survival rate of lung adenocarcinoma.A UBE2F-knockout lung adenocarcinoma cell line was constructed us-ing CRISPR/Cas9 technology,and a UBE2F-knockout lung adenocarcinoma metastasis model was con-structed in nude mice to verify the effect of UBE2F knockout on lung adenocarcinoma metastasis.The effects of UBE2F knockout on invasion and migra-tion of lung adenocarcinoma cells were examined by cell scratch assay and Transwell invasion and mi-gration assays.The effect of down-regulated UBE2F expression on snail expression,a key marker of epi-thelial-mesenchymal transition(EMT),was detect-ed by Western blot and Real time PCR.RESULTS:Multiple database analysis showed that UBE2F was highly expressed in lung cancer,and Kaplan-Meier Plotter analysis showed that high expression of UBE2F in lung adenocarcinoma had better progno-sis than low expression.In vivo experiments showed that compared with control group,the number of nodules metastasized on the lung sur-face of nude mice after UBE2F knockout was signifi-cantly increased(P<0.05).Cell scratch assay and Transwell assay showed that UBE2F enhanced the migration and invasion ability of lung cancer cells after knockout,and the difference were statistically significant(P<0.05).Western blot and Real time PCR results indicated that the level of EMT tran-scription factor snail protein and mRNA increased after UBE2F knockout.CONCLUSION:In lung ade-nocarcinoma cells,UBE2F down-regulation leads to Snail accumulation and promotes invasion and me-tastasis of lung adenocarcinoma cells.
