An Enhancer LncRNA Regulates NFE2 Expression and Proliferation in Human Leukemic K562 Cells
10.16476/j.pibb.2023.0105
- VernacularTitle:人NFE2基因上游增强子lncRNA调控NFE2基因转录和K562细胞增殖
- Author:
Yan-Fei LU
1
;
Song-Ya QU
1
;
Jing-Jing ZHU
1
;
Chao LIU
1
;
Jian WANG
1
;
Bing-She HAN
1
;
Jun-Fang ZHANG
1
Author Information
1. Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China
- Publication Type:Journal Article
- Keywords:
NFE2;
enhancer;
lncRNA;
cellular proliferation
- From:
Progress in Biochemistry and Biophysics
2024;51(1):190-201
- CountryChina
- Language:English
-
Abstract:
ObjectiveTranscription factor NFE2 was observed abnormal expression in myeloproliferative neoplasm (MPN) patients. However, how NFE2 is transcriptionally regulated remains ambiguous. This study aims to explore the elements and molecular mechanisms involved in the transcriptional regulation of NFE2. MethodsActive enhancers were predicted by public NGS data and conformed experimentally via dual luciferase reporter assay. After that, PRO-seq and GRO-seq data was used to detect enhancer RNAs transcribed from these enhancers. RACE was utilized to clone the full length enhancer RNA (eRNA) transcripts, and RT-qPCR was used to measure their expression in different leukemia cell lines as well as the transcript levels during induced differentiation. Finally, to investigate the molecular function of the eRNA, overexpression and knockdown of the eRNA via lentivirus system was performed in K562 cells. ResultsWe identified three enhancers regulating NFE2 transcription, which located at -3.6k, -6.2k and +6.3k from NFE2 transcription start site (TSS) respectively. At the -3.6k enhancer, we cloned an eRNA transcript and characterized that as a lncRNA which was expressed and located in the nucleus in three types of leukemia cell lines. When this lncRNA was overexpressed, expression of NFE2 was upregulated and decreases of K562 cell proliferation and migration ability were observed. While knocking down of this lncRNA, the level of NFE2 decreases correspondingly and the proliferation ability of K562 cells increases accordingly. ConclusionWe identified an enhancer lncRNA that regulates NFE2 transcription positively and suppresses K562 cell proliferation.
