MAPK8 mediates resistance to temozolomide and apoptosis of glioblastoma cells through MAPK signaling pathway

Xu, Peng; Hou, Shuangxing; Sha, Longgui

doi:10.1016/j.biopha.2018.06.084

Cited by 42 publications

(31 citation statements)

References 25 publications

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“…This pathway regulates a broad range of physiological processes such as cell growth, proliferation, differentiation, migration development, inflammatory responses and apoptosis (28) for cells in general, and the progression, invasion, survival and drug resistance in the context of cancer cells. Xu et al demonstrated that MAPK8 promoted resistance to anticancer drug, accelerated cell proliferation and inhibited the apoptosis of glioblastoma cells via activating the MAPK signaling pathway (29). Other studies have reported that in tumor tissue samples derived from patient, extracellular signal-regulated protein kinase (ERK) was phosphorylated, indicating that this survival pathway was active in glioma cells (30).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Profiling of 3D Glioblastoma Tumoroids for the Identification of Mechanisms Involved in Anticancer Drug Resistance

Chaicharoenaudomrung

Kunhorm

Promjantuek

et al. 2019

In Vivo

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Background/Aim: Among various types of brain tumors, glioblastoma is the most malignant and highly aggressive brain tumor that possesses a high resistance against anticancer drugs. To understand the underlined mechanisms of tumor drug resistance, a new and more effective research approach is required. The three dimensional (3D) in vitro cell culture models could be a potential approach to study cancer features and biology, as well as screen for anticancer agents due to the close mimicry of the 3D tumor microenvironments. Materials and Methods: With our developed 3D alginate scaffolds, Ilumina RNA-sequencing was used to transcriptomically analyze and compare the gene expression profiles between glioblastoma cells in traditional 2-dimensional (2D) monolayer and in 3D Ca-alginate scaffolds at day 14. To verify the reliability and accuracy of Illumina RNA-Sequencing data, ATP-binding cassette transporter genes were chosen for quantitative real-time polymerase chain reaction) verification. Results: The results showed that 7,411 and 3,915 genes of the 3D glioblastoma were up-regulated and down-regulated, respectively, compared with the 2D-cultured glioblastoma. Furthermore, the Kyoto Encyclopaedia of Genes and Genomes pathway analysis revealed that genes related to the cell cycle and DNA replication were enriched in the group of down-regulated gene. On the other hand, the genes involved in mitogen-activated protein kinase signaling, autophagy, drug metabolism through cytochrome P450, and ATP-binding cassette transporter were found in the up-regulated gene collection. Conclusion: 3D glioblastoma tumoroids might potentially serve as a powerful platform for exploring glioblastoma biology. They can also be valuable in anti-glioblastoma drug screening, as well as the identification of novel molecular targets in clinical treatment of human glioblastoma.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Profiling of 3D Glioblastoma Tumoroids for the Identification of Mechanisms Involved in Anticancer Drug Resistance

Chaicharoenaudomrung

Kunhorm

Promjantuek

et al. 2019

In Vivo

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“…KRAS is active in most glioblastomas and necessary for the persistence of glioblastoma tumors in mouse models 57 . It also triggers the oncogenic pathway of MAPK (RAS/RAF/MEK/ERK) in glioblastoma 58 . So, the downregulation of PIK3CA, PIK3CB, KRAS, EGFR, and MYC proteins by miR-429 in our study, suggests a tumor suppressor effect of miR-429 in GBM cell lines.…”

Section: Discussionmentioning

confidence: 99%

miR-429 Suppresses Proliferation and Migration in Glioblastoma Cells and Induces Cell-cycle Arrest via Modulating Several Target Genes of ERBB Signaling Pathway

Gheidari

Arefian

Kabiri

et al. 2021

Preprint

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Glioblastoma is aggressive and lethal brain cancer, which is incurable by cancer standard treatments. miRNAs have great potential to be used for gene therapy due to their ability to modulate several target genes simultaneously. We found miR-429 is downregulated in glioblastoma and has several predicted target genes from the ERBB signaling pathway using bioinformatics tools. ERBB is the most over-activated genetic pathway in glioblastoma patients, which is responsible for augmented cell proliferation and migration in glioblastoma multiforme (GBM). Here we overexpressed miR-429 using lentiviral vectors in GBM U-251 cells and observed that the expression level of several oncogenes of the ERBB pathway, EGFR, PIK3CA, PIK3CB, KRAS, and MYC significantly decreased; as shown by real-time PCR and western blotting. Using the luciferase assay, we showed that miR-429 directly targets MYC, BCL2, and EGFR. In comparison to scrambled control, miR-429 had a significant inhibitory effect on cell proliferation and migration as deduced from MTT and scratch wound assays and induced cell-cycle arrest in flow cytometry. Altogether miR-429 seems to be an efficient suppressor of the ERBB genetic signaling pathway and a potential therapeutic for glioblastoma.

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“…MAPK1 is a direct target gene of miR-585 that promotes the proliferation and metastasis of gastric cancer [23] .MAPK8, which is also known as JNK, is characterized as a pronounced marked protein, is an important cellular pathway triggered in response to DNA damage, and it was also proved to be associated with tumor progression, including cell survival, migration and autophagy [24] . Sun et al [25] reported that MAPK8 could mediate S/G2 phase cycle arrest and apoptosis, and suppress AKT activation in gastric cancer cells, and dysregulated MAPK8 was observed in several cancers, such as glioblastoma, skin cancer, brain tumor and leukemia [26,27] .…”

Section: Discussionmentioning

confidence: 99%

Effect and mechanism of Acoritataninowii Rhizoma and Curcumae Radix on chronic gastritis: a network pharmacology study

Zhang¹,

Dai²,

Li³

et al. 2020

Preprint

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Background Chronic gastritis (CG) is an inflammatory disease which is one of the common diseases of the digestive system. To investigate the mechanisms of herbal pair Acoritataninowii Rhizoma(Shichangpu, AR) and Curcumae Radix༈Yujin, CR༉ in treatment of CG based on the network pharmacology. Methods The possible active ingredients and targets of AR-CR were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The UniProt database was used to query the human gene corresponding to each target protein. The genes related to CG were collected from the GeneCards database, the OMIM database, the DisGeNET database and the PharmGKB database. Intersected the target genes of AR-CR and CG, then protein-protein interaction(PPI) network was constructed by STRING website. The overlapped genes were subjected to gene ontology༈GO༉enrichment and Kyoto encyclopedia of genes and genomes༈KEGG༉pathway enrichment analyses by David. Results 45 intersection genes were obtained, and there were 40 targets in the PPI network for protein interaction, the kernel targets with Degree ≥ 10 included AKT1, TNF, JUN, MAPK3, MAPK8 and MAPK1. The Go enrichment analysis was mainly related to protein binding, enzyme binding, protein homodimerization activity, etc. The KEGG pathway enrichment analyses mainly involved the Pathways in cancer, TNF signaling pathway, Apoptosis, and VEGF signaling pathway. Conclusion AR-CR might delayed, blocked or reversed the atrophy, intestinal metaplasia, dysplasia and canceration of gastric mucosa by targeting key proteins and signal pathways,achieved the effect of the treatment of CG.

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MAPK8 mediates resistance to temozolomide and apoptosis of glioblastoma cells through MAPK signaling pathway

Cited by 42 publications

References 25 publications

Transcriptomic Profiling of 3D Glioblastoma Tumoroids for the Identification of Mechanisms Involved in Anticancer Drug Resistance

Transcriptomic Profiling of 3D Glioblastoma Tumoroids for the Identification of Mechanisms Involved in Anticancer Drug Resistance

miR-429 Suppresses Proliferation and Migration in Glioblastoma Cells and Induces Cell-cycle Arrest via Modulating Several Target Genes of ERBB Signaling Pathway

Effect and mechanism of Acoritataninowii Rhizoma and Curcumae Radix on chronic gastritis: a network pharmacology study

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