Inhibition of c-REL using siRNA increased apoptosis and decreased proliferation in pre-B ALL blasts: Therapeutic implications

Mohammadi, Seyedeh Momeneh; Mohammadnejad, Daryoush; Feizi, Abbas Ali Hosseinpour; Movassaghpour, Ali Akbar; Montazersaheb, Soheila; Charoudeh, Hojjatollah Nozad

doi:10.1016/j.leukres.2017.08.012

Cited by 6 publications

(2 citation statements)

References 48 publications

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“…The Glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ) gene was used as an internal reference gene for the normalization of gene expression levels. As with previous research, the following gene-specific primers were used: GAPDH , forward: 5′-AGAAGGTGGTGAAGCAGGC-3′ and reverse: 5′-TCCACCACCCAGTTGCTG-3′; REL , forward: 5′-GAATCAATCCATTCAATGTCCC-3′ and reverse: 5′-AAGAGCAGTCGTCAAATTACC-3′; SOD2 , forward: 5′-GACAAACCTCAGCCCTAACG-3′ and reverse: 5′-CGTCAGCTTCTCCTTAAACTTG-3′ ( 41 , 42 ). The gene expression levels were calculated using the 2 ΔΔCT method and normalized to the mRNA levels of GAPDH .…”

Section: Methodsmentioning

confidence: 99%

hsa-miR-518-5p/hsa-miR-3135b Regulates the REL/SOD2 Pathway in Ischemic Cerebral Infarction

Zhao

Jiang

2022

Front. Neurol.

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ObjectivesIschemic cerebral infarction (ICI) is a fatal neurovascular disorder. A bioinformatics approach based on single-cell and bulk RNA-seq analyses was applied to investigate the pathways and genes involved in ICI and study the expression profile of these genes.MethodsFirst, the aberrantly regulated “small-molecule ribonucleic acids” [microRNA (miRNAs)] and messenger RNAs (mRNAs) were analyzed using transcriptome data from the ischemic brain infarction dataset of the Gene Expression Omnibus (GEO) database. In mouse cerebrovascular monocytes, the single-cell regulatory network inference and clustering (SCENIC) workflow was used to identify key transcription factors (TFs). Then, the two miRNA-TF-mRNA interaction networks were constructed. Moreover, the molecular complex detection (MCODE) extracted the core sub-networks and identified the important TFs within these sub-networks. Finally, whole blood samples were collected for validation of the expression of critical molecules in ICI.ResultsWe identified four cell types and 266 regulons in mouse cerebrovascular monocytes using SCENIC analysis. Moreover, 112 differently expressed miRNAs and 3,780 differentially expressed mRNAs were identified. We discovered potential biomarkers in ICI by building a miRNA-TF-mRNA interaction network. The hsa-miR-518-5p/hsa-miR-3135b/REL/SOD2 was found to play a potential role in ICI progression. The expression of REL and superoxide dismutase 2 (SOD2) was significantly elevated in the ICI group in the clinical cohort (P < 0.05). Furthermore, a REL expression was elevated in endothelial cells and fibroblasts at the single-cell level, indicating that REL is a cell-specific regulon. Functional enrichment analyses revealed that REL is primarily engaged in neurotransmitter activity and oxidative phosphorylation.ConclusionsOur research uncovered novel biomarkers for ICI of neurovascular disease. The hsa-miR-518-5p/hsa-miR-3135b may regulate the REL/SOD2 pathway in ICI progression.

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Section: Methodsmentioning

confidence: 99%

hsa-miR-518-5p/hsa-miR-3135b Regulates the REL/SOD2 Pathway in Ischemic Cerebral Infarction

Zhao

Jiang

2022

Front. Neurol.

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“…In this process, siRNA after creation and binding to the RISC complex, degrades target mRNA through connecting to particular sequences on the target mRNA (Kim, Lee, Harris, Nakahara, & Carthew, ). Using of siRNA for silencing of specific target gene is current approach in gene therapy and varied cancer cells treatment, containing lung, leukemia, colorectal, melanoma, and prostate cancer cell lines (Boia‐Ferreira et al, ; Emons et al, ; Lai et al, ; Mohammadi et al, ; Sanlioglu, Karacay, Koksal, Griffith, & Sanlioglu, ). Recently, various types of siRNA have been used for treatment of TRAIL‐resistant cancer cell lines, for example, in the human prostate cancer cell lines, DU145 and LNCaP that expressed high level of DcR2, siRNA down‐regulated the surface expression of DcR2 and consequently improved the sensitivity of prostate cancer cell lines to TRAIL(Sanlioglu et al, ).…”

Section: Intracellular Anti‐apoptotic Proteins As Targeted Therapymentioning

confidence: 99%

Down‐regulation of intracellular anti‐apoptotic proteins, particularly c‐FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL

Hassanzadeh

Hagh

Alivand

et al. 2018

Journal Cellular Physiology

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily that induces apoptosis in different types of cancer cells via activation of caspase cascade. TRAIL interacts with its cognate receptors that placed on cancer cells surface, including TRAIL-R1 (death receptor 4, DR4), TRAIL-R2 (death receptor 5, DR5), TRAIL-R3 (decoy receptor 1, DcR1), TRAIL-R4 (decoy receptor 2, DcR2), and osteoprotegerin (OPG). Despite high apoptosis-inducing ability of TRAIL, various cancerous cells gain resistance to TRAIL gradually, and consequently TRAIL potential for apoptosis stimulation in these cells diminishes intensely. According to diverse ranges of examinations, intracellular anti-apoptotic proteins, such as cellular-FLICE inhibitory protein (c-FLIP), apoptosis inhibitors (IAPs), myeloid cell leukemia sequence 1 (MCL-1), BCL-2, BCL-XL, and survivin play key role in cancer cells resistance to TRAIL. These proteins attenuate cancer cells sensitivity to TRAIL via various functions, importantly through caspase cascade suppression. The c-FLIP avoids from caspase 8 activation by FADD via binding to caspase 8 cleavage of FADD. Moreover, it activates signaling pathways that involved in cancer cells survival and proliferation. Intriguingly, it appears that the down-regulation of intracellular anti-apoptotic proteins, particularly c-FLIP is effectiveness goal for TRAIL-resistant cancers therapy, because their up-regulation in association with poor prognosis has been observed in various types of TRAIL-resistant cancers. In this review, we tried to collect and examine investigations that researchers have been able to sensitize cancer cells to TRAIL through targeting of c-FLIP alone or with other intracellular anti-apoptotic proteins directly or indirectly. It seems that co-treatment of resistant cells by TRAIL with other therapeutic agents with the aim of intracellular anti-apoptotic proteins inhibition is hopeful and attractive approach to overcome various TRAIL-resistant cancers.

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Design, mechanism, delivery and therapeutics of canonical and Dicer-substrate siRNA

Raja

Katas

Amjad

2019

Asian Journal of Pharmaceutical Sciences

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Inhibition of c-REL using siRNA increased apoptosis and decreased proliferation in pre-B ALL blasts: Therapeutic implications

Cited by 6 publications

References 48 publications

hsa-miR-518-5p/hsa-miR-3135b Regulates the REL/SOD2 Pathway in Ischemic Cerebral Infarction

hsa-miR-518-5p/hsa-miR-3135b Regulates the REL/SOD2 Pathway in Ischemic Cerebral Infarction

Down‐regulation of intracellular anti‐apoptotic proteins, particularly c‐FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL

Design, mechanism, delivery and therapeutics of canonical and Dicer-substrate siRNA

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