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Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes
Published on: April 12, 2015
lncRNA-Map2k4 sequesters miR-199a to promote FGF1 expression and spinal cord neuron growth
1Department of Traumatic Orthopedics, The Fifth Affiliated Hospital of GuangZhou Medical University, 621# Harbour Road, Whampoa District, GuangZhou 510700, Guangdong Province, China.
Abstract:
Spinal cord injury (SCI) is a common critical illness in clinical practice. SCI prevention, treatment and rehabilitation have become important topics in today's medical profession. Studies have shown that long noncoding RNAs (lncRNAs) also play an important role in the pathology of SCI. The biology software analysis identified miR-199a binding sites in the lncRNA-Map2k4 and FGF1 sequences, which were confirmed by the subsequent dual luciferase reporter assay. When lncRNA-Map2k4 expression was down-regulated by siRNA, miR-199a expression in neurons was up-regulated and FGF1 expression was down-regulated. In turn, miR-199a up-regulation inhibited lncRNA-Map2k4 and FGF1 expression. But when lncRNA-Map2k4-m (a lncRNA-Map2k4 overexpression vector with mutated miR-199a binding sites) was co-transfected into neuronal cells with miR-199a mimics, lncRNA-Map2k4-m over-expression did not block the inhibition of FGF1 expression by miR-199a. Moreover, lncRNA-Map2k4 and FGF1 promoted the proliferation and inhibited the apoptosis of neuronal cells, whereas miR-199a down-regulated the aforementioned functions of lncRNA-Map2k4 and FGF1; however, lncRNA-Map2k4-m could not block the inhibitory action of miR-199a on proliferation. Thus, lncRNA-Map2k4 regulates neuronal proliferation and apoptosis through a miR-199a/FGF1 pathway. This finding provides more evidence for the role of lncRNAs in SCI.
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