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Neuroglobin promotes neurogenesis through Wnt signaling pathway.

ABSTRACT: Neuroglobin (Ngb) has been demonstrated by our lab and others to be neuroprotective against neurological disorders including stroke. However, the roles of Ngb in neurogenesis remain elusive. Neurogenesis can occur in adulthood and can be induced by pathological conditions in the brain such as stroke, and significantly contributes to functional recovery, thus enhancing endogenous neurogenesis may be a promising therapeutic strategy for neurodegenerative diseases. In this study we aimed to investigate the roles of Ngb in neurogenesis using Lentivirus overexpressing Ngb (Lv-Ngb). We show that Ngb overexpression promoted the proliferation of neural progenitor cells (NPC) marked by increased neurosphere number and size. Ngb overexpression also enhanced neuronal differentiation of cultured NPC under differentiation conditions. Moreover, subventricular injection of Lv-Ngb in mice after middle cerebral artery occlusion (MCAO) increased PSA-NCAM positive neuroblastoma cells and Tuj1 positive immature neurons, suggesting that Ngb overexpression promotes neurogenesis in mice brain after stroke. We further show that the pro-neurogenesis effect of Ngb overexpression might be mediated through Dvl1 up-regulation, and subsequent activation of Wnt signaling, indicated by increased nuclear localization of beta-catenin. These results suggest that Ngb may play an important role in promoting neurogenesis in neurodegenerative diseases such as stroke, which may eventually benefit the development of stroke therapeutics targeting neurogenesis through Ngb upregulation.

SUBMITTER: Yu Z

PROVIDER: S-EPMC6147998 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Neuroglobin promotes neurogenesis through Wnt signaling pathway.

Yu Zhanyang Z Cheng Chongjie C Liu Yu Y Liu Ning N Lo Eng H EH Wang Xiaoying X

Cell death & disease 20180920 10

Neuroglobin (Ngb) has been demonstrated by our lab and others to be neuroprotective against neurological disorders including stroke. However, the roles of Ngb in neurogenesis remain elusive. Neurogenesis can occur in adulthood and can be induced by pathological conditions in the brain such as stroke, and significantly contributes to functional recovery, thus enhancing endogenous neurogenesis may be a promising therapeutic strategy for neurodegenerative diseases. In this study we aimed to investi ...[more]

PMID: 30237546

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Project description:BACKGROUND:40-50% of colorectal cancer (CRC) patients develop metastatic disease; the presence of metastasis hinders the effective treatment of cancer through surgery, chemotherapy and radiotherapy, which makes 5-year survival rate extremely low; therefore, studying CRC metastasis is crucial for disease therapy. In the present study, we investigated the role of rhomboid domain containing 1 (RHBDD1) in tumor metastasis of CRC. METHODS:The expression of RHBDD1 was analyzed in 539 colorectal tumor tissues for its correlation with lymphatic metastasis and distal metastasis. Transwell assay in vitro and pleural metastasis analysis in vivo were performed to determine the functions of RHBDD1 during CRC cells metastasis. RNA-seq analysis, TOP/FOP flash reporter assay, western blot and transwell assay were performed to investigate the underlying mechanism for the function of RHBDD1 on Wnt signaling pathway. Bioinformatics analysis was conducted to investigate epithelial-mesenchymal transition (EMT) and stemness in HCT-116 cells. Tissue microarray analysis, Q-PCR and western blot were performed to determine the correlation of RHBDD1 and Zinc Finger E-Box Binding Homeobox 1 (ZEB1). RESULTS:In this study, we found that RHBDD1 expression was positively correlated with lymphatic metastasis and distal metastasis in 539 colorectal tumor tissues. RHBDD1 expression can promote CRC cells metastasis in vitro and in vivo. RNA-Seq analysis showed that the Wnt signaling pathway played a key role in this metastatic regulation. RHBDD1 mainly regulated ser552 and ser675 phosphorylation of ?-catenin to activate the Wnt signaling pathway. Rescuing ser552 and ser675 phosphorylation of ?-catenin resulted in the recovery of signaling pathway activity, migration, and invasion in CRC cells. RHBDD1 promoted EMT and a stem-like phenotype of CRC cells. RHBDD1 regulated the Wnt/?-catenin target gene ZEB1, a potent EMT activator, at the RNA and protein levels. Clinically, RHBDD1 expression was positively correlated with ZEB1 at the protein level in 71 colon tumor tissues. CONCLUSIONS:Our findings therefore indicated that RHBDD1 can promote CRC metastasis through the Wnt signaling pathway and ZEB1. RHBDD1 may become a new therapeutic target or clinical biomarker for metastatic CRC.

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Neuroglobin promotes neurogenesis through Wnt signaling pathway.

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Neuroglobin promotes neurogenesis through Wnt signaling pathway.

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