LncRNA BDNF-AS suppresses colorectal cancer cell proliferation and migration by epigenetically repressing GSK-3β expression.

Abstract

This study was designed to investigate the molecular mechanism and biological roles of long non-coding RNA (lncRNA) brain-derived neurotrophic factor antisense (BDNF-AS) in colorectal cancer (CRC). The quantitative real-time PCR (qRT-PCR) and western blotting were performed to detect the expressions of lncRNA BDNF-AS and glycogen synthase kinase-3β (GSK-3β) in human CRC tissues and cell lines. The cell proliferation, transwell migration, and invasion assays were carried out to evaluate the effect of lncRNA BDNF-AS on the growth of CRC cells. RNA pull-down and RNA immunoprecipitation (RIP) assays were conducted to confirm the interaction between lncRNA BDNF-AS and enhancer of Zeste Homologue 2 (EZH2). Chromatin immunoprecipitation (ChIP) assay was used to verify the enrichment of EZH2 and histone H3 lysine 27 trimethylation (H3K27me3) in the promoter region of GSK-3β in CRC cells. LncRNA BDNF-AS expression was significantly decreased, while GSK-3β was highly expressed in human CRC tissues and cell lines. Moreover, lncRNA BDNF-AS induced inhibition of proliferation, migration, and invasion of CRC cells via inhibiting GSK-3β expression. Mechanistically, BDNF-AS led to GSK-3β promoter silencing in CRC cells through recruitment of EZH2. In conclusion, lncRNA BDNF-AS functioned as an oncogene in CRC and shed new light on lncRNA-directed therapeutics in CRC. SIGNIFICANCE OF THE STUDY: LncRNA BDNF-AS is recently reported to be remarkably downregulated in a variety of tumours and served as a tumour suppressor. However, the functions and underlying mechanism of lncRNA BDNF-AS in CRC pathogenesis have not been reported yet. Our study is the first to demonstrate the effect of lncRNA BDNF-AS in CRC and revealed that lncRNA BDNF-AS expression is negatively correlated with the aggressive biological behaviour of CRC. Further investigation demonstrated that lncRNA BDNF-AS functioned as a tumour suppressor in CRC progression by suppressing GSK-3β expression through binding to EZH2 and H3K27me3 with the GSK-3β promoter, shedding light on the diagnosis and therapy for CRC.

• Authors: Hui Zhi, Jiayu Lian
• Journal: Cell biochemistry and function (Cell Biochem Funct) Vol. 37 Issue 5 Pg. 340-347 (Jul 2019) ISSN: 1099-0844 [Electronic] England
• PMID: 31062382 (Publication Type: Journal Article)
• Copyright: © 2019 John Wiley & Sons, Ltd.

Chemical References

• Brain-Derived Neurotrophic Factor
• RNA, Long Noncoding
• Glycogen Synthase Kinase 3 beta

Topics

• Brain-Derived Neurotrophic Factor (genetics)
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Colorectal Neoplasms (genetics, pathology)
• Epigenesis, Genetic (genetics)
• Gene Expression Regulation, Neoplastic
• Glycogen Synthase Kinase 3 beta (biosynthesis, deficiency, genetics)
• HCT116 Cells
• Humans
• RNA, Long Noncoding (genetics, metabolism)