Dataset Information

LncRNA Neat1 mediates miR-124-induced activation of Wnt/?-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/?-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/?-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/?-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.

SUBMITTER: Cui Y

PROVIDER: S-EPMC6921476 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Cui Yi Y Yin Yanyun Y Xiao Zhifeng Z Zhao Yannan Y Chen Bing B Yang Bin B Xu Bai B Song Hongwei H Zou Yunlong Y Ma Xu X Dai Jianwu J

Stem cell research & therapy 20191218 1

<h4>Background</h4>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.<h4>Materials and methods</h4>In order to explore the function of miR-124 in neural differentiation, the molecular markers (Tuj1, Map2, and GFAP) correlated wit ...[more]

PMID: 31852544

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Project description:The incidence of thyroid nodules has been increasing worldwide; however, there are currently no feasible and robust methods to differentiate malignant thyroid nodules from benign thyroid nodules. The present study aimed to establish a practical method to determine the malignancy of thyroid nodules. Reverse transcription‑quantitative PCR and western blot analyses were performed to compare the levels of long non‑coding RNA nuclear enriched abundant transcript 1 (NEAT1), microRNA (miR)‑9, miR‑124, PTEN and programmed cell death protein 6 (PDCD6) in the peripheral blood and thyroid tissue samples between patients with malignant and benign thyroid nodules. Additionally, a regulatory relationship between NEAT1, miR‑124, miR‑9, PTEN and PDCD6 was established in the present study. The diagnostic value of NEAT1, miR‑124 and miR‑9 was determined using a ROC analysis. The expression levels of NEAT1, PTEN and PDCD6 in peripheral blood and thyroid tissue samples collected from the benign group were higher compared with those in the malignant group, whereas the expression levels of miR‑124 and miR‑9 were lower in the benign group. In the peripheral blood, NEAT1 expression exhibited an area under the curve (AUC) value of 0.8546, whereas miR‑124 and miR‑9 expression had AUC values of 0.7657 and 0.7019, respectively. In the thyroid tissue, NEAT1, miR‑124, and miR‑9 had AUC values of 0.9304, 0.8221 and 0.7757, respectively. Additionally, miR‑9 and miR‑124 expression levels in BCPaP and SW579 cells was decreased after transfection with a NEAT1 expression vector compared with those in cells transfected with the control vector, whereas the expression of PTEN and PDCD6 was upregulated. By contrast, transfection with short hairpin RNA targeting NEAT1 notably increased the expression of miR‑9 and miR‑124 while downregulating the expression of PTEN and PDCD6 compared with that in the control cells. In conclusion, the results of the present study demonstrated that the dysregulation of NEAT1 expression may be used to differentiate benign and malignant thyroid nodules.