miR‐34a/BCL‐2 signaling axis contributes to apoptosis in MPP+‐induced SH‐SY5Y cells

Shanesazzade, Zahra; Peymani, Maryam; Ghaedi, Kamran; Nasr-Esfahani, Mohammad Hossein

doi:10.1002/mgg3.469

Cited by 31 publications

(14 citation statements)

References 18 publications

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“…Previous studies reported that miR-34a re-expression could repress proliferation and promote apoptosis by regulation of Bcl-2 29,30. Since the aforementioned results revealed that ISOV reduced the expression of Bcl-2 protein in vivo, we examined if the effects of ISOV on proliferation, apoptosis and stem-like features of OSLCs were involved in the regulation of Bcl-2 by miR-34a.…”

Section: Resultsmentioning

confidence: 94%

“…Furthermore, the exact mechanism by which ISOV promotes apoptotic cell death in OSLCs has not been clarified. Considering that Bcl-2, a mitochondrion-associated anti-apoptotic protein, was directly regulated by miR-34a,28–30 the purpose of the present study was to examine th e in vivo and in vitro multiplication inhibitory activities and the corresponding apoptosis inducing effects of ISOV in OSLCs. Furthermore, we aimed to investigate the potential mechanisms associated with these processes, notably with regard to the involvement of epigenetic regulations in OS cells.…”

Section: Introductionmentioning

confidence: 99%

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Isovitexin Suppresses Cancer Stemness Property And Induces Apoptosis Of Osteosarcoma Cells By Disruption Of The DNMT1/miR-34a/Bcl-2 Axis

Liang¹,

Xu²,

Cao³

et al. 2019

CMAR

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BackgroundIsovitexin (apigenin-6-C-glucoside, ISOV) is a natural flavonoid that exhibits tumor suppressive activity on various types of cancer. However, it is unknown whether the mechanism of its action in osteosarcoma (OS) is associated with epigenetic regulation and whether it involves DNA methyltransferase 1 (DNMT1), microRNAs and their targets.Materials and methodsThe present study investigated the effects of ISOV on DNMT1 activation and miR-34a and Bcl-2 expression levels in order to explain the mechanism underlying ISOV-mediated repression of proliferation and stemness. In addition, the induction of apoptosis in the spheres derived from OS cells was investigated.ResultsThe results indicated that ISOV significantly repressed survival, induced apoptosis and decreased the level of CD133, CD44, ABCG2 and ALDH1 mRNA in the spheres derived from U2OS (U2OS-SC) and MG63 cells (MG63-SC). ISOV further reduced the sphere formation rate of U2OS-SC and MG63-SC. It is important to noted that, ISOV inhibited tumor growth and reduced tumor size of U2OS-SC xenografts in nude mice, which was accompanied by decreased CD133 protein levels, elevated apoptotic index, downregulation of proliferating cell nuclear antigen (PCNA) expression, reduced DNMT1 activity and expression, increased miR-34a and decreased Bcl-2 levels. We identified that Bcl-2 as a direct functional target of miR-34a. Furthermore, ISOV exhibited a synergistic effect with 5-aza-2′-deoxycytidine, the miR-34a mimic or ABT-263 in order to repress cell survival, induce apoptosis, downregulate CD133, CD44, ABCG2 and ALDH1 mRNA expression levels and reduce sphere formation rates of U2OS-SC and MG63-SC cells.ConclusionThe findings suggested that ISOV-mediated epigenetic regulation involved the DNMT1/miR-34a/Bcl-2 axis and caused the suppression of stemness and induction of apoptosis in the spheres derived from OS cells. The data indicated that ISOV exhibited a novel efficient potential for the treatment of OS.

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Section: Resultsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Isovitexin Suppresses Cancer Stemness Property And Induces Apoptosis Of Osteosarcoma Cells By Disruption Of The DNMT1/miR-34a/Bcl-2 Axis

Liang¹,

Xu²,

Cao³

et al. 2019

CMAR

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“…The analysis of microRNA expression showed the downregulated profile of miR-34bc associated with pathological brain tissue in different clinical stages of PD [37,74]. Although reduction of miR-34bc expression in differentiated dopaminergic neuronal cells results in a moderate reduction in cell viability, it was accompanied by altered mitochondrial function [75]. DJ1 and Parkin were also shown to be miR-34bc indirect targets [74].…”

Section: Brain Pathology and Micrornasmentioning

confidence: 99%

MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer

Godlewski

Lenart

Salińska

2019

ncRNA

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The mammalian brain is made up of billions of neurons and supporting cells (glial cells), intricately connected. Molecular perturbations often lead to neurodegeneration by progressive loss of structure and malfunction of neurons, including their death. On the other side, a combination of genetic and cellular factors in glial cells, and less frequently in neurons, drive oncogenic transformation. In both situations, microenvironmental niches influence the progression of diseases and therapeutic responses. Dynamic changes that occur in cellular transcriptomes during the progression of developmental lineages and pathogenesis are controlled through a variety of regulatory networks. These include epigenetic modifications, signaling pathways, and transcriptional and post-transcriptional mechanisms. One prominent component of the latter is small non-coding RNAs, including microRNAs, that control the vast majority of these networks including genes regulating neural stemness, differentiation, apoptosis, projection fates, migration and many others. These cellular processes are also profoundly dependent on the microenvironment, stemness niche, hypoxic microenvironment, and interactions with associated cells including endothelial and immune cells. Significantly, the brain of all other mammalian organs expresses the highest number of microRNAs, with an additional gain in expression in the early stage of neurodegeneration and loss in expression in oncogenesis. However, a mechanistic explanation of the concept of an apparent inverse correlation between the odds of cancer and neurodegenerative diseases is only weakly developed. In this review, we thus will discuss widespread de-regulation of microRNAome observed in these two major groups of brain pathologies. The deciphering of these intricacies is of importance, as therapeutic restoration of pre-pathological microRNA landscape in neurodegeneration must not lead to oncogenesis and vice versa. We thus focus on microRNAs engaged in cellular processes that are inversely regulated in these diseases. We also aim to define the difference in microRNA networks between pro-survival and pro-apoptotic signaling in the brain.

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“…J o u r n a l P r e -p r o o f (Carro et al, 2010;Mi et al, 2018;Packer et al, 2008;Schonrock et al, 2012;Schraivogel et al, 2011;Song et al, 2013;X. Tan et al, 2012) miR-34abc GBM, PD, AD (Leone et al, 2017;Mi et al, 2018;Min˜ones-Moyano et al, 2011;Modi et al, 2015;Navarro & Lieberman, 2015;Shanesazzade et al, 2018) miR-29 GBM, PD, AD, HD (Ihle & Abraham, 2017;Morita et al, 2013;Roshan et al, 2014;Saito & Saito, 2012;Tumaneng et al, 2012) miR-124 GBM, PD, HD (An et al, 2013;Conti et al, 2012;Fowler et al, 2011;Johnson & Buckley, 2009;Makeyev et al, 2007;Mucaj et al, 2014;Saraiva et al, 2016;Silber et al, 2008;Xie et al, 2012) miR-128 GBM, PD, AD, MS oxidative response (Rostamian et al, 2018;Schonrock et al, 2012). Upregulation of miR-9 has been associated with PD and AD pathology with its pro-apoptotic functions.…”

Section: Disorder Mirnasmentioning

confidence: 99%

“…In general, miR-34bc was downregulated in PD. In dopaminergic neurons downregulation of miR-34bc along with mitochondrial dysfunction caused cellular J o u r n a l P r e -p r o o f death (Shanesazzade et al, 2018). Considering the facts, miR-34abc could be a potent therapeutic target in different brain pathologies.…”

Section: Mir-34abcmentioning

confidence: 99%

Nutraceutical regulation of miRNAs involved in neurodegenerative diseases and brain cancers

Ghosh

Kumar

Mukherjee

et al. 2021

Heliyon

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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miR‐34a/BCL‐2 signaling axis contributes to apoptosis in MPP⁺‐induced SH‐SY5Y cells

Abstract: miR-34a and its target gene, BCL-2, play a possible role in the induction of apoptosis in DA neurons, and therefore, they have a potential role in the pathogenesis of PD. Consequently, the therapeutic potential of miR-34a could be considered in order to inhibit the progression of PD.

Cited by 31 publications

References 18 publications

<p>Isovitexin Suppresses Cancer Stemness Property And Induces Apoptosis Of Osteosarcoma Cells By Disruption Of The DNMT1/miR-34a/Bcl-2 Axis</p>

<p>Isovitexin Suppresses Cancer Stemness Property And Induces Apoptosis Of Osteosarcoma Cells By Disruption Of The DNMT1/miR-34a/Bcl-2 Axis</p>

MicroRNA in Brain pathology: Neurodegeneration the Other Side of the Brain Cancer

Nutraceutical regulation of miRNAs involved in neurodegenerative diseases and brain cancers

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