Presentation Authors: Bin Xu, Nanjing, China, People's Republic of, Ruifang Liu, Buffalo, NY, Ming Chen, Nanjing, China, People's Republic of, Dean G. Tang*, Buffalo, NY
Introduction: Long noncoding RNAs (lncRNAs) have been implicated in many biological processes and mainly function through epigenetic mechanisms. Our previous study, comparing prostate basal and luminal cells via RNA-seq analysis, found that over 20% of the differentially expressed transcripts are lncRNAs.To explore the biological function and molecular mechanism of dysregulated lncRNAs in prostate cancer (PCa)
Methods: The change of maternal expressed gene 3 (MEG3) gene level in PCa patients was analyzed from multiple dimensions and databases. The consequence of MEG3 dysregulation was determined by its influence on cell proliferation, metastasis and interacting with target genes.Tumor suppressive function was measured through in vivo tumor regeneration assay and in vitro cell viability and mobility assays. The interaction of MEG3 and target was tested by RNA immunoprecipitation (RIP) and RNA pulldown assays. Statistical difference and variances were determined by Student t test or Chi-squared test.
Results: MEG3 is predominantly expressed in human prostate basal cells when compared to prostate luminal cells and PCa tissues and its loss of expression significantly correlated with metastasis, higher clinical stage, and poor overall survival of PCa patients. Additionally, MEG3 overexpression suppressed PCa cell proliferation, colony and sphere formation, and metastasis. Furthermore, loss of MEG3 lessened the suppressive function of EZH2, including a stronger suppression to EZH2 repressed genes (MKX, ADRB2, CDKN2A, DAB2IP) and increased expression of EZH2 induced gene (CCND1).
Conclusions: We found MEG3 loss is common among PCa patients. MEG3 plays tumor suppressive function in PCa may via interacting with EZH2 and fine-tuning its target gene.