NRSN2 promotes breast cancer metastasis by activating PI3K/AKT/mTOR and NF‑κB signaling pathways

Ren, Fei; Zhang, Wei; Lü, Shan; Ren, Hong; Guo, Yantong

doi:10.3892/ol.2019.11152

Cited by 12 publications

(10 citation statements)

References 24 publications

(26 reference statements)

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“… 36 Overexpressing NRSN2 is concerned with malignant phenotype of cancers, such as ovarian cancer 37 and breast cancer. 38 In this study, the binding relationships between MALAT1 and miR-143, and miR-143 and NRSN2 were confirmed using dual-luciferase reporter gene assay. miR-143 expression was downregulated and NRSN2 expression was upregulated in EVs-treated osteosarcoma cells.…”

Section: Discussionsupporting

confidence: 52%

Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Vesicles Promote Proliferation, Invasion and Migration of Osteosarcoma Cells via the lncRNA MALAT1/miR-143/NRSN2/Wnt/β-Catenin Axis

Li¹,

Chen²,

Shang³

et al. 2021

OTT

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Introduction Osteosarcoma is a malignant primary bone tumor. Bone marrow-derived mesenchymal stem cells-derived extracellular vesicles (BMSC-EVs) bear repair function for bone and cartilage. This study investigated the mechanism of BMSC-EVs in osteosarcoma cell proliferation, migration and invasion. Methods BMSC-EVs were isolated and identified. The effects of different concentrations of EVs on osteosarcoma cell proliferation, migration and invasion were evaluated. LncRNA MALAT1 expression in osteosarcoma cells was detected. BMSCs were transfected with si-MALAT1 or si-NC. The binding relationships between MALAT1 and miR-143, and miR-143 and NRSN2 were verified. Levels of NRSN2 and Wnt/β-catenin pathway key proteins were detected. miR-143 mimic was transfected into EVs-treated osteosarcoma cells. Nude mice were injected with MG63 cells to verify the effect of EVs on osteosarcoma growth in vivo. Results BMSC-EVs facilitated proliferation, invasion and migration of osteosarcoma cells. BMSC-EVs carried MALAT1 into osteosarcoma cells. BMSC-EVs-treated osteosarcoma cells showed increased MALAT1 and NRSN2 expressions, decreased miR-143 expression, and activated Wnt/β-catenin pathway. miR-143 mimic or si-MALAT1 reversed the effects of BMSC-EVs on osteosarcoma cells. In vivo experiment confirmed that BMSC-EVs promoted tumor growth in nude mice. Discussion BMSC-EVs promoted proliferation, invasion and migration of osteosarcoma cells via the MALAT1/miR-143/NRSN2/Wnt/β-catenin axis. This study might offer new insights into osteosarcoma management.

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Section: Discussionsupporting

confidence: 52%

Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Vesicles Promote Proliferation, Invasion and Migration of Osteosarcoma Cells via the lncRNA MALAT1/miR-143/NRSN2/Wnt/β-Catenin Axis

Li¹,

Chen²,

Shang³

et al. 2021

OTT

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“…As the downstream molecules, mTOR and NF‐κB were found to exhibit potential reciprocal regulation in tumor cells (Radhakrishnan et al, 2013; Ren et al, 2020; Tanaka et al, 2011; Wu et al, 2016). It has been shown that mTOR is able to positively mediate the activity of NF‐κB by stimulating the activation of IKK (inhibitor of κB kinase) in tumor cells (Dan et al, 2008; Zeng, Yin, et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

The interactions between mTOR and NF‐κB: A novel mechanism mediating mechanical stretch‐stimulated osteoblast differentiation

Wang

Cai

Zeng

et al. 2020

Journal Cellular Physiology

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Mechanical stretch is known to promote osteoblast differentiation in vitro and accelerate bone regeneration in vivo, whereas the relevant mechanism remains unclear. Recent studies have shown the importance of reciprocal interactions between mammalian target of rapamycin (mTOR) and nuclear factor kappa B (NF-κB; two downstream molecules of Akt) in the regulation of tumor cells. Thus, we hypothesize that mTOR and NF-κB as well as their interconnection play a critical role in mediating stretch-induced osteogenic differentiation in osteoblasts. We herein found that mechanical stretch (10% elongation at six cycles/min) significantly promoted the expression of osteoblast differentiation-related markers (including ALP, BMP2, Col1α, OCN, and Runx2) in osteoblast-like MG-63 cells, accompanied by increased mTOR phosphorylation and NF-κB p65 phosphorylation and nuclear translocation. Blockade of mTOR by antagonist or small interfering RNA suppressed osteogenesis-related gene expression in response to mechanical stretch, whereas inhibition of NF-κB further increased stretch-induced osteoblast differentiation. Moreover, inhibition of mTOR decreased the phosphorylation of NF-κB, and blockade of NF-κB reduced the mTOR activation in MG63 cells under mechanical stretch. Coinhibition of mTOR and NF-κB abolishes the alteration of osteogenic differentiation induced by single mTOR or NF-κB inhibition under mechanical stretch, which is equivalent to the noninhibition level for osteoblasts under mechanical stretch. The expression levels of osteogenic differentiation in osteoblasts after inhibition of Akt were similar to those after co-inhibition of mTOR and NF-κB under mechanical stretch. This study for the first time reveals the reciprocal interconnection between mTOR and NF-κB in osteoblasts under mechanical stretch and indicates that mTOR and NF-κB as well as their interactions play a key role in the regulation of cellular homeostasis of osteoblasts in response to mechanical stretch. These findings are helpful for enriching our basic knowledge of the molecular mechanisms of osteoblast mechanotransduction, and also providing insight

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“…Its postnatal neuronal expression indicates that it might regulate synaptic functions [49]. Several studies in cancer models suggest that Neurensin-2 regulates the PI3K/AKT/mTOR pathway in an unknown mechanism [50][51][52]. In the context of depression, this pathway is specifically implicated in the induction of the synaptic translation of AMPAR and its incorporation into the postsynaptic membrane to form new synapses [13].…”

Section: Antidepressants and Neurensin-2 Modulate Ampar Signaling In mentioning

confidence: 99%

Activation of the p11/SMARCA3/Neurensin-2 pathway in parvalbumin interneurons mediates the response to chronic antidepressants

et al. 2021

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The delayed behavioral response to chronic antidepressants depends on dynamic changes in the hippocampus. It was suggested that the antidepressant protein p11 and the chromatin remodeling factor SMARCA3 mediate this delayed response by inducing transcriptional changes in hippocampal neurons. However, what target genes are regulated by the p11/SMARCA3 complex to mediate the behavioral response to antidepressants, and what cell type mediates these molecular changes remain unknown. Here we report that the p11/SMARCA3 complex represses Neurensin-2 transcription in hippocampal parvalbumin-expressing interneurons after chronic treatment with Selective Serotonin Reuptake Inhibitors (SSRI). The behavioral response to antidepressants requires upregulation of p11, accumulation of SMARCA3 in the cell nucleus, and a consequent repression of Neurensin-2 transcription in these interneurons. We elucidate a functional role for p11/SMARCA3/Neurensin-2 pathway in regulating AMPA-receptor signaling in parvalbumin-expressing interneurons, a function that is enhanced by chronic treatment with SSRIs. These results link SSRIs to dynamic glutamatergic changes and implicate p11/SMARCA3/Neurensin-2 pathway in the development of more specific and efficient therapeutic strategies for neuropsychiatric disorders.

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NRSN2 promotes breast cancer metastasis by activating PI3K/AKT/mTOR and NF‑κB signaling pathways

Cited by 12 publications

References 24 publications

Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Vesicles Promote Proliferation, Invasion and Migration of Osteosarcoma Cells via the lncRNA MALAT1/miR-143/NRSN2/Wnt/β-Catenin Axis

Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Vesicles Promote Proliferation, Invasion and Migration of Osteosarcoma Cells via the lncRNA MALAT1/miR-143/NRSN2/Wnt/β-Catenin Axis

The interactions between mTOR and NF‐κB: A novel mechanism mediating mechanical stretch‐stimulated osteoblast differentiation

Activation of the p11/SMARCA3/Neurensin-2 pathway in parvalbumin interneurons mediates the response to chronic antidepressants

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