LncRNA Neat1 mediates miR-124-induced activation of Wnt/β-catenin signaling in spinal cord neural progenitor cells

Abstract

Background: Emerging evidence suggests that miR-124 performs important biological functions in neural stem cells (NSCs); it regulates NSC behavior and promotes the differentiation of NSCs into neurons, but the exact molecular mechanism remains unknown. And also, the role of miR-124 during spinal cord injury regeneration is unclear. Materials and methods: In order to explore the function of miR-124 in neural differentiation, the molecular markers (Tuj1, Map2, and GFAP) correlated with the differentiation of NSCs were detected by immunofluorescence staining both in cultured mouse spinal cord progenitor cells (SC-NPCs) and in spinal cord injury (SCI) animal models. The migration ability and apoptosis of cultured SC-NPCs were also evaluated by Transwell migration assay and TUNEL assay. In addition, the relative expression of lnRNA Neat1-and Wnt/β-catenin signaling-related genes were detected by quantitative real-time PCR. Results: In this study, we revealed that lncRNA Neat1 is involved in regulating Wnt/β-catenin signaling that is activated by miR-124 in SC-NPCs. LncRNA Neat1 was also found to play an important role in regulating neuronal differentiation, apoptosis, and migration of SC-NPCs. Furthermore, we demonstrated that overexpression of miR-124 resulted in elevated Neat1 expression, accompanied with the functional recovery of locomotion in a mouse model of spinal cord injury. Conclusions: Our results confirm the therapeutic effectiveness of miR-124 on the functional recovery of injured spinal cord, supporting the rationale and feasibility of miR-124 for spinal cord injury treatment in future clinical therapy. Furthermore, we concluded that the miR-124-Neat1-Wnt/β-catenin signaling axis is involved in regulating the cell function of SC-NPCs, and this may offer novel therapeutic avenues for future treatment of SCI.

Hypoxic preconditioning ameliorated neuronal injury after middle cerebral artery occlusion by promoting neurogenesis

“…The cell migration assay was mainly conducted with reference to a previous publication (Cui et al., 2019). Briefly, NSCs were incubated in a hypoxic and glucose‐free environment for 3, 5, 8, and 10 hr.…”

DPYSL2 is a novel regulator for neural stem cell differentiation in rats: revealed by Panax notoginseng saponin administration

“…The development of the NSC therapy is therefore restricted, meaning the mechanisms of the NSC differentiation into neurons need to be elucidated [15]. So far, many signals and genes were demonstrably involved in the process of NSC differentiation, such as the bHLH gene, Notch signal, Wnt signal, MAPK signal, and even some micro-RNAs [5,12,45,46,54]. However, the effective regulation involving in Chinese medicine for the NSC differentiation is complex and demands exploration.…”

Downregulation of Long Non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 Inhibits MEG-01 Differentiation and Platelet-Like Particles Activity

“…This finding indicated that NEAT1 could promote the differentiation of NB4 cells (Zeng et al, 2014). In addition, NEAT1 increased during the differentiation of many kinds of cells, including embryonic stem cells, muscle cells, nerve cells, and glial cells (Lehnert et al, 2007;Mercer et al, 2010;Billing et al, 2019;Cui et al, 2019;Wang et al, 2019). NEAT1 has been shown to be highly expressed in hematopoietic stem cells, progenitors, and immune cells.…”