Long nonding RNA UCA1 regulates neural stem cell differentiation by controlling miR-1/Hes1 expression

Neural stem cells are able to self-renew and generate glial and neuronal lineages. Neural stem cell may serve as therapeutic method for neurological disorders including spinal cord injuries, Parkinson's disease, Huntington's disease and Alzheimer's disease. Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides with limited protein-coding capacity. Recent studies have demonstreated that lncRNAs play an important role in several cellular processes including cell differentiation, cell development, proliferation, apoptosis, invasion and migration. However, the role of lncRNA human urothelial carcinoma associated 1 (UCA1) in the development of neural stem cells remains unknown. In this study, we showed that the expression of UCA1 was upregulated in the neural stem cell in a time-dependent manner. Knockdown of UCA1 suppressed the neural stem cell proliferation. Inhibition of UCA1 decreased the expression of nestin and the formation of neurosphere. Moreover, knockdown of UCA1 suppressed the neural stem cell differentiation to astrocyte and promoted the neural stem cell differentiation to neuron. Furthermore, we demonstrated that knockdown of UCA1 increased the expression of miR-1 in the neural stem cell and suppressed the expresion of Hes1, which is one target gene of miR-1. In addition, ectopic expression of Hes1 could impair siUCA1-induced neural stem cells proliferation. Overexpression of Hes1 suppressed siUCA1-induced β-tubulin expression and promoted siUCA1-inhibited GFAP expression in the neural stem cell. These results suggested that UCA1 regulated the neural stem cell proliferation and differentiation through regulating Hes1 expression.