Long non-coding RNA C2dat1 regulates CaMKIIδ expression to promote neuronal survival through the NF-κB signaling pathway following cerebral ischemia

Xu, Qiaobing; Deng, Feihong; Xing, Zumin; Wu, Zhuomin; Cen, Bohong; Xu, Shaohua; Zhao, Zhenlong; Nepomuceno, Rachel; Bhuiyan, Mohammad Iqbal Hossain; Sun, Dandan; Wang, Qiming J.; Ji, Aimin

doi:10.1038/cddis.2016.57

Cited by 106 publications

(123 citation statements)

References 44 publications

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“…For the control cells that were either untransfected (UT) or transfected with an empty vector (vec), OGD/R treatment resulted in progressive neuronal cell death that maximized at about 48 h (30% cell death), in line with previous reports [12]. In contrast, overexpression of CaMKIIδ significantly enhanced cell survival in both N2a (Fig.…”

Section: Camkiiδ and Camkiiγ Promoted Neuronal Survival In Response Tsupporting

confidence: 71%

“…Our previous study confirmed that C2dat1-induced CaMKIIδ expression promoted neuronal survival through the activation of the NF-κB signaling pathway [12]. To determine if C2dat2 acted through the same signaling mechanisms, both C2dat1 and C2dat2 were depleted in N2a cells and primary neurons followed by OGD/R.…”

Section: Camkiiδ Acted Through the Nf-κb Signaling Pathway To Promotementioning

confidence: 71%

“…con, control 13-15 and exon 14 of CAMK2D on mouse chromosome 3. C2dat1 has been shown to modulate CaMKIIδ expression in response to I/R [12]. Here, we report the identification of a 2nd novel CAMK2D-associated lncRNA, CAMK2D-associated transcript 2 (C2dat2).…”

Section: Camkiiδ and Camkiiγ Promoted Neuronal Survival In Response Tmentioning

confidence: 89%

“…Although we had shown previously that C2dat1-mediated CAMK2D upregulation acts through the NF-κB signaling pathway [12], the function and signaling mechanism of CAMK2D per se have not been examined. Here, we showed that overexpression of CaMKIIδ promoted the activation of NF-κB signaling pathway.…”

Section: Camkiiδ Acted Through the Nf-κb Signaling Pathway To Promotementioning

confidence: 99%

“…C2dat1 is induced by I/R and targets CAMK2D for upregulation in murine neuronal cells and mouse I/R models. Increased CaMKIIδ promotes neuronal survival by activating the NF-κB signaling pathway [12]. Compared to CaMKIIδ, CAMK2G/CaMKIIγ is a less-known member of the CaMKII family and its role in the CNS has just begun to emerge.…”

Section: Introductionmentioning

confidence: 99%

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Ischemic Injury-Induced CaMKIIδ and CaMKIIγ Confer Neuroprotection Through the NF-κB Signaling Pathway

Das

Roy

et al. 2018

Mol Neurobiol

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Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) has long been implicated in neuronal injury caused by acute ischemia/ reperfusion (I/R). However, its precise role and regulatory mechanisms remain obscure. Here, we investigated the role of the CaMKII family in neuronal survival during I/R. Our data indicated that CAMK2D/CaMKIIδ and CAMK2G/CaMKIIγ were selectively upregulated in a time-dependent manner at both transcriptional and protein levels after acute ischemia. Overexpression of CaMKIIδ promoted neuronal survival, while their depletion exacerbated ischemic neuronal death. Similar to CaMKIIδ, knockdown of CAMKIIγ resulted in significant neuronal death after I/R. We further identified CaMKIIδ 2 as the subtype that is selectively induced by I/R in primary neurons. The induction of CaMKIIδ was controlled in part by a pair of long non-coding RNAs (lncRNAs), C2dat1 and C2dat2. C2dat2, similar to C2dat1, was upregulated by I/R and cooperated with C2dat1 to modulate CaMKIIδ expression. Knockdown of C2dat1/2 blocked OGD/R-induced CaMKIIδ expression and decreased neuronal survival but did not affect the levels of CaMKIIγ, indicating specific targeting of CAMK2D by C2dat1/2. Mechanistically, I/R-induced CaMKIIδ and CaMKIIγ caused the upregulation of IKKα/β and further activation of the NF-κB signaling pathway to protect neurons from ischemic damage. Genetically, downregulating p65 subunit of NF-κB in mice increased I/R-induced neuronal death by blocking the activity of CaMKII/IKK/IκBα/NF-κB signaling axis. In summary, CaMKIIδ and CaMKIIγ are novel I/R-induced genes that promote neuronal survival during ischemic injury. The upregulation of these CaMKII kinases led to activation of the NF-κB signaling pathway, which protects neurons from ischemic damage.

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Section: Camkiiδ and Camkiiγ Promoted Neuronal Survival In Response Tsupporting

confidence: 71%

Section: Camkiiδ Acted Through the Nf-κb Signaling Pathway To Promotementioning

confidence: 71%

Section: Camkiiδ and Camkiiγ Promoted Neuronal Survival In Response Tmentioning

confidence: 89%

Section: Camkiiδ Acted Through the Nf-κb Signaling Pathway To Promotementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ischemic Injury-Induced CaMKIIδ and CaMKIIγ Confer Neuroprotection Through the NF-κB Signaling Pathway

Das

Roy

et al. 2018

Mol Neurobiol

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The exo‐microRNA (miRNA) signaling pathways in pathogenesis and treatment of stroke diseases: Emphasize on mesenchymal stem cells (MSCs)

Farahmand,

Nabiuni,

Vafaei Mastanabad

et al. 2024

Cell Biochemistry & Function

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A major factor in long‐term impairment is stroke. Patients with persistent stroke and severe functional disabilities have few therapy choices. Long noncoding RNAs (lncRNAs) may contribute to the regulation of the pathophysiologic processes of ischemic stroke as shown by altered expression of lncRNAs and microRNA (miRNAs) in blood samples of acute ischemic stroke patients. On the other hand, multipotent mesenchymal stem cells (MSCs) increase neurogenesis, and angiogenesis, dampen neuroinflammation, and boost brain plasticity to improve functional recovery in experimental stroke models. MSCs can be procured from various sources such as the bone marrow, adipose tissue, and peripheral blood. Under the proper circumstances, MSCs can differentiate into a variety of mature cells, including neurons, astrocytes, and oligodendrocytes. Accordingly, the capability of MSCs to exert neuroprotection and also neurogenesis has recently attracted more attention. Nowadays, lncRNAs and miRNAs derived from MSCs have opened new avenues to alleviate stroke symptoms. Accordingly, in this review article, we examined various studies concerning the lncRNAs and miRNAs' role in stroke pathogenesis and delivered an overview of the therapeutic role of MSC‐derived miRNAs and lncRNAs in stroke conditions.

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Tumor microenvironment and noncoding RNAs as co‐drivers of epithelial–mesenchymal transition and cancer metastasis

Alsibai

Meseure

2017

Developmental Dynamics

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Reciprocal interactions between cancer cells and tumor microenvironment (TME) are crucial events in tumor progression and metastasis. Pervasive stromal reprogramming of TME modifies numerous cellular functions, including extracellular matrix (ECM) stiffness, inflammation, and immunity. These environmental factors allow selection of more aggressive cells that develop adaptive strategies associating plasticity and epithelial-mesenchymal transition (EMT), stem-like phenotype, invasion, immunosuppression, and resistance to therapies. EMT is a morphomolecular process that endows epithelial tumor cells with mesenchymal properties, including reduced adhesion and increased motility. Numerous studies have demonstrated involvement of noncoding RNAs (ncRNAs), such as miRNAs and lncRNAs, in tumor initiation, progression, and metastasis. NcRNAs regulate every hallmark of cancer and have now emerged as new players in induction and regulation of EMT. The reciprocal regulatory interactions between ncRNAs, TME components, and cancer cells increase the complexity of gene expression and protein translation in cancer. Thus, deeper understanding of molecular mechanisms controlling EMT will not only shed light on metastatic processes of cancer cells, but enhance development of new therapies targeting metastasis. In this review, we will provide recent findings on the role of known ncRNAs relevant to EMT and cancer metastasis and discuss the role of the interaction between ncRNAs and TME as co-drivers of EMT. Developmental Dynamics 247:405-431, 2018. V C 2017 Wiley Periodicals, Inc.

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Long non-coding RNA C2dat1 regulates CaMKIIδ expression to promote neuronal survival through the NF-κB signaling pathway following cerebral ischemia

Cited by 106 publications

References 44 publications

Ischemic Injury-Induced CaMKIIδ and CaMKIIγ Confer Neuroprotection Through the NF-κB Signaling Pathway

Ischemic Injury-Induced CaMKIIδ and CaMKIIγ Confer Neuroprotection Through the NF-κB Signaling Pathway

The exo‐microRNA (miRNA) signaling pathways in pathogenesis and treatment of stroke diseases: Emphasize on mesenchymal stem cells (MSCs)

Tumor microenvironment and noncoding RNAs as co‐drivers of epithelial–mesenchymal transition and cancer metastasis

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