BRG1 promotes chemoresistance of pancreatic cancer cells through crosstalking with Akt signalling

Liu, Xiaoran; Tian, Xiaodong; Wang, Rui; Ma, Yue; Kornmann, Marko; Yang, Yinmo

doi:10.1016/j.ejca.2014.05.017

Cited by 41 publications

(33 citation statements)

References 25 publications

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“…Brg1 has been reported to be an important gene in regulating cell apoptosis. Brg1 has been reported to inhibit the apoptosis of various cancer cells by regulating p53 and PTEN/Akt signaling . In this study, we found that upregulation of Brg1 by miR‐144‐3p inhibition significantly promotes cell viability and inhibits apoptosis of neurons.…”

Section: Discussionmentioning

confidence: 60%

Suppression of microRNA‐144‐3p attenuates oxygen–glucose deprivation/reoxygenation‐induced neuronal injury by promoting Brg1/Nrf2/ARE signaling

Zhao

Cheng

et al. 2018

J Biochem & Molecular Tox

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Accumulating evidence has reported that microRNA-144-3p (miR-144-3p) is highly related to oxidative stress and apoptosis. However, little is known regarding its role in cerebral ischemia/reperfusion-induced neuronal injury. Herein, our results showed that miR-144-3p expression was significantly downregulated in neurons following oxygen-glucose deprivation and reoxygenation (OGD/R) treatment. Overexpression of miR-144-3p markedly reduced cell viability, promoted cell apoptosis, and increased oxidative stress in neurons with OGD/R treatment, whereas downregulation of miR-144-3p protected neurons against OGD/R-induced injury. Brahma-related gene 1 (Brg1) was identified as a potential target gene of miR-144-3p. Moreover, downregulation of miR-144-3p promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased antioxidant response element (ARE) activity. However, knockdown of Brg1 significantly abrogated the neuroprotective effects of miR-144-3p downregulation. Overall, our results suggest that miR-144-3p contributes to OGD/R-induced neuronal injury in vitro through negatively regulating Brg1/Nrf2/ARE signaling.

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Section: Discussionmentioning

confidence: 60%

Suppression of microRNA‐144‐3p attenuates oxygen–glucose deprivation/reoxygenation‐induced neuronal injury by promoting Brg1/Nrf2/ARE signaling

Zhao

Cheng

et al. 2018

J Biochem & Molecular Tox

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“…Most of the genes constituting this panel serve as biomarkers for efficacy, prognosis, diagnosis, disease progression (targeting inflammation, oxidative stress and vesiculation gene networks) and response to therapy [43,44,45,46,47,48,49,50,51,52,53,54,55,56,57]. Vitamin D mediated genetic networks such as those identified in our study, for example inflammation, oxidative stress and membrane vesicle biogenesis pathways in 143B cells, shed insight into the mechanism(s) underlying antineoplastic effects of vitamin D in human OS.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells

Garimella

Tadikonda

Tawfik

et al. 2017

IJMS

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Osteosarcoma (OS) is an aggressive malignancy of bone affecting children, adolescents and young adults. Understanding vitamin D metabolism and vitamin D regulated genes in OS is an important aspect of vitamin D/cancer paradigm, and in evaluating vitamin D as adjuvant therapy for human OS. Vitamin D treatment of 143B OS cells induced significant and novel changes in the expression of genes that regulate: (a) inflammation and immunity; (b) formation of reactive oxygen species, metabolism of cyclic nucleotides, sterols, vitamins and mineral (calcium), quantity of gap junctions and skeletogenesis; (c) bone mineral density; and (d) cell viability of skeletal cells, aggregation of bone cancer cells and exocytosis of secretory vesicles. Ingenuity pathway analysis revealed significant reduction in Runx2 target genes such as fibroblast growth factor -1, -12 (FGF1 and FGF12), bone morphogenetic factor-1 (BMP1), SWI/SNF related, matrix associated actin dependent regulator of chromatin subfamily a, member 4 (SMARCA4), Matrix extracellular phosphoglycoprotein (MEPE), Integrin, β4 (ITGBP4), Matrix Metalloproteinase -1, -28 (MMP1 and MMP28), and signal transducer and activator of transcription-4 (STAT4) in vitamin D treated 143B OS cells. These genes interact with the inflammation, oxidative stress and membrane vesicle biogenesis gene networks. Vitamin D not only inhibited the expression of Runx2 target genes MMP1, MMP28 and kallikrein related peptidase-7 (KLK7), but also migration and invasion of 143B OS cells. Vitamin D regulated Runx2 target genes or their products represent potential therapeutic targets and laboratory biomarkers for applications in translational oncology.

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“…However, our results show that it may be critical to define the stage and origin of the PDA when exploring this chemotherapeutic route. A recent report further demonstrated that high Brg1 expression is associated with gemcitabine resistance, a property also exhibited by increased expression of Hmga2 (Liu et al 2014). Therefore, specific targeting of the Brg1-Hmga2 axis may be beneficial to reduce EMT-related tumor aggressiveness and also sensitize resistant tumors to chemotherapy.…”

Section: G12dmentioning

confidence: 99%

“…Several studies, including ours, have shown that low Brg1 expression is correlated with poor prognosis von Figura et al 2014). However, contrasting reports also exist demonstrating high Brg1 association with reduced overall survival (Liu et al 2014). It is important to consider that the above-mentioned clinical specimens are all PDA samples without any knowledge of the preinvasive lesions from which these tumors have originated; for example, duct or acinar cells.…”

Section: G12dmentioning

confidence: 99%

Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation

et al. 2015

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Pancreatic ductal adenocarcinoma (PDA) develops predominantly through pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) precursor lesions. Pancreatic acinar cells are reprogrammed to a "ductal-like" state during PanIN-PDA formation. Here, we demonstrate a parallel mechanism operative in mature duct cells during which functional cells undergo "ductal retrogression" to form IPMN-PDA. We further identify critical antagonistic roles for Brahma-related gene 1 (Brg1), a catalytic subunit of the SWI/SNF complexes, during IPMN-PDA development. In mature duct cells, Brg1 inhibits the dedifferentiation that precedes neoplastic transformation, thus attenuating tumor initiation. In contrast, Brg1 promotes tumorigenesis in fullblown PDA by supporting a mesenchymal-like transcriptional landscape. We further show that JQ1, a drug that is currently being tested in clinical trials for hematological malignancies, impairs PDA tumorigenesis by both mimicking some and inhibiting other Brg1-mediated functions. In summary, our study demonstrates the contextdependent roles of Brg1 and points to potential therapeutic treatment options based on epigenetic regulation in PDA.

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BRG1 promotes chemoresistance of pancreatic cancer cells through crosstalking with Akt signalling

Cited by 41 publications

References 25 publications

Suppression of microRNA‐144‐3p attenuates oxygen–glucose deprivation/reoxygenation‐induced neuronal injury by promoting Brg1/Nrf2/ARE signaling

Suppression of microRNA‐144‐3p attenuates oxygen–glucose deprivation/reoxygenation‐induced neuronal injury by promoting Brg1/Nrf2/ARE signaling

Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells

Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation

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