Abstract
Maternally Expressed Gene 3 (MEG3) encodes a lncRNA which is suggested to function as a tumor suppressor. Previous studies suggested that MEG3 functioned through activation of p53, however, the functional properties of MEG3 remain obscure and their relevance to human diseases is under continuous investigation. Here, we try to illuminate the relationship of MEG3 and p53, and the consequence in hepatoma cells. We find that transfection of expression construct of MEG3 enhances stability and transcriptional activity of p53. Deletion analysis of MEG3 confirms that full length and intact structure of MEG3 are critical for it to activate p53-mediated transactivation. Interestingly, our results demonstrate for the first time that MEG3 can interact with p53 DNA binding domain and various p53 target genes are deregulated after overexpression of MEG3 in hepatoma cells. Furthermore, results of qRT-PCR have shown that MEG3 RNA is lost or reduced in the majority of HCC samples compared with adjacent non-tumorous samples. Ectopic expression of MEG3 in hepatoma cells significantly inhibits proliferation and induces apoptosis. In conclusion, our data demonstrates that MEG3 functions as a tumor suppressor in hepatoma cells through interacting with p53 protein to activate p53-mediated transcriptional activity and influence the expression of partial p53 target genes.
Highlights
IntroductionNcRNAs are functional RNA molecules that are not translated into proteins, including transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), microRNAs (miRNAs), small nucleolar RNAs (snoRNAs), Piwi-RNAs and long non-coding RNAs (lncRNAs) [1]
NcRNAs are functional RNA molecules that are not translated into proteins, including transfer RNAs, ribosomal RNAs, microRNAs, small nucleolar RNAs, Piwi-RNAs and long non-coding RNAs [1]
Through bioinformatics analysis of microarray data, compared with 287 p53 target genes whose data come from transcriptional regulatory element database (TRED) [25, 26], we found 34 of these p53 target genes showed consequent changes in gene expression in stable cell line overexpressing Maternally Expressed Gene 3 (MEG3) (Tables 1 and 2) including 21 up-regulated genes which principally involved in negative regulation of apoptosis, cell death, cell cycle and cell proliferation and 13 down-regulated genes which mainly participated in positive regulation of cell cycle and DNA replication
Summary
NcRNAs are functional RNA molecules that are not translated into proteins, including transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), microRNAs (miRNAs), small nucleolar RNAs (snoRNAs), Piwi-RNAs and long non-coding RNAs (lncRNAs) [1]. LncRNAs which are widely distributed in mammals, are a class of RNA molecules with
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