Background: Long non-coding RNAs (lncRNA) have been shown to play important roles in human cancer. We examined expression, prognostic potential and functional roles of lncRNA, brain-derived neurotrophic factor antisense (BDNF-AS) in human retinoblastoma (RB).
Methods: BDNF-AS expression in RB tumors was characterized according to the clinicopathological parameters of patients. BDNF-AS mRNA level was compared between RB tumors and normal retinas, as well as RB cell lines and normal retinal epithelial cells. RB patients' overall survival was compared between those with low and high BDNF-AS tumor expressions. Statistical analysis was performed to examine the independence of BDNF-AS being cancer biomarker in RB. In Y79 and WERI-Rb-1 cells, BDNF-AS was upregulated. It's effect on cancer proliferation, migration and cell-cycle transition were assessed.
Results: BDNF-AS is downregulated in RB tumors and cell lines. Low BDNF-AS expression in RB tumors is correlated with patients' advanced clinical stage and tumor differentiation status. Low BDNF-AS expression is associated with shorter overall survival and may be acting as an independent marker in RB. In Y79 and WERI-Rb-1 cells, forced overexpression of BDNF-AS inhibited cancer proliferation and migration. It also induced cell-cycle arrest at G0/G1 phase by downregulating CDC42, Cyclin E and BDNF.
Conclusion: BDNF-AS is lowly expressed, and may be used as a prognostic biomarker in RB. Upregulating BDNF-AS has inhibitory effect on RB development, probably through the suppression of cell-cycle transition.
Keywords: BDNF-AS; Biomarker; CDC42; Overall survival; Retinoblastoma; lncRNA.
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