Background
Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) is crucial in the association of diabetes mellitus (DM) and hepatocellular carcinoma (HCC), and estrogen receptor 1 (ESR1) plays an essential role in various cancers. However, the underlying regulatory effect of ESR1/lncRNA MEG3 on HCC with DM remains unclear. This study explored the regulatory effect of ESR1/lncRNA MEG3 on HCC cell progression.
Conclusions
ESR1 inhibits HCC cell progression through positively regulating lncRNA MEG3, and the results provide a promising strategy for HCC management.
Methods
Bioinformatics analysis was used to predict the promoter sequence of lncRNA MEG3 using UCSC (http://genome.ucsc.edu/), followed by luciferase reporter and RNA immunoprecipitation (RIP) assays to verify the specific combination between ESR1 and lncRNA MEG3 promoter. After cotransfection with ESR1, ESR1 siRNA or lncRNA MEG3 RNA, CCK-8, 5-ethynyl-2'-deoxyuridine (EdU) and colony formation assays were used to evaluate the cell proliferation capacity. Cell apoptosis was assessed using flow cytometry analysis. Next, wound healing and Transwell assays were conducted to examine cell invasiveness and migration. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were performed to quantify the expression of ESR1 or lncRNA MEG3.
Results
ESR1 might be the transcription factor (TF) of lncRNA MEG3, and ESR1 bound with lncRNA MEG3 promoter. Overexpression of ESR1 repressed the proliferation, migration and invasion of HepG2 cells, and promoted apoptosis of HepG2 cells under high glucose conditions. Silencing ESR1 decreased lncRNA MEG3 expression in HepG2 cells but enhanced proliferation, migration and invasion. Meanwhile, a rescue assay demonstrated that silencing lncRNA MEG3 reversed the inhibitory effect of ESR1 on HepG2 cell progression. Conclusions: ESR1 inhibits HCC cell progression through positively regulating lncRNA MEG3, and the results provide a promising strategy for HCC management.