Expression of insulin-like growth factor binding protein genes and its hypoxic regulation in U87 glioma cells depends on ERN1 mediated signaling pathway of endoplasmic reticulum stress

Do, Myoung‐Sool; Ap, Kharkova; Ll, Karbovskyi; Oh, Myounghak

doi:10.4149/endo_2015_02_73

Cited by 33 publications

(41 citation statements)

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“…Th e changes in these genes expression in cells without IRE1 signaling enzyme function possible contribute in the suppression of glioma cell proliferation and tumor growth, because there are data indicating that the estrogen receptor related factors play an important role in the control of cell proliferation and apoptosis (Cho et al 2010;Lapierre et al 2015;Tiwari et al 2015). It is possible that increased expression of FAM162A, PGRMC2, TRIM16 and SLC39A6 genes as well as decreased expression of ESRRA, and NRIP1 genes (Figure 1) may contribute to the suppression of the proliferation and glioma growth from glioma cells with IRE1 knockdown (Auf et al 2010(Auf et al , 2013Aziz et al 2015;Casaburi et al 2015;Minchenko et al 2015;Zhang et al 2015;Matsushima et al 2016). Th erefore, suppressing of NRIP1, which modulates transcriptional activity of the estrogen receptor, as well as knockdown of a site-specifi c transcription regulator ESRRA/NR3B1 inhibits growth of the cancer cells in vitro and in vivo (Aziz et al 2015;Matsushima et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…It is important for evaluation of possible signifi cance of these genes in the control of glioma growth through ER stress signaling mediated by IRE1 and hypoxia. It is known that stress signaling pathways are involved in numerous metabolic pathways and inhibition of the activity of IRE1 signaling enzyme in glioma cells had antitumor eff ects (Auf et al 2010(Auf et al , 2013Manie et al 2014;Minchenko et al 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Th e expression levels of NRIP1 (nuclear receptor interacting protein 1), FAM162F/E2IG5 (family with sequence similarity 162 member A/E2-induced gene 5 protein), TRIM16/EBBP (tripartite motif containing 16/estrogen-responsive B box protein), ESRRA/NR3B1 (estrogen related receptor alpha/nuclear receptor subfamily 3 group B member 1), PGRMC2/PMBP (progesterone receptor membrane component 2/progesterone membrane binding protein), and SLC39A6/LIV-1 (solute carrier family 39 member 6/estrogen regulated protein LIV-1) mRNAs as well as ACTB mRNA were measured in control U87 glioma cells and cells with a defi ciency of IRE1 by quantitative polymerase chain reaction in realtime using qPCR "RotorGene RG-3000" (Corbett Research, Germany) and Applied Biosystems 7500 (Applied Biosystems, U.S.A.) using SYBRGreen Mix (ABgene, Th ermo Fisher Scientifi c, Epsom, Surrey, UK). QuaniTect Reverse Transcription Kit (QIAGEN, Hilden, Germany) was used for cDNA synthesis as described previously (Minchenko et al 2015). Polymerase chain reaction was performed in triplicate.…”

Section: Methodsmentioning

confidence: 99%

“…Th e ER stress response-signaling pathway mediated by IRE1 is tightly associated with hypoxia and linked to the neovascularization, tumor growth, and cell death processes as well as to suppression of insulin receptor signaling through activation of c-Jun N-terminal kinase (Lenihan and Taylor 2013;Clarke et al 2014;Minchenko et al 2015). Recent studies have confi rmed the existence of a crosstalk between the estrogen receptors and UPR (Rajapaksa et al 2016).…”

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confidence: 99%

“…Th e ER stress is mediated by three sensor and signaling pathways, but inositol requiring enzyme 1 (IRE1/ERN1) is a central mediator of the unfolded protein response and an important component of tumor growth, because its inhibition leads to a suppression of glioma growth through down-regulation of the angiogenesis and proliferation processes (Drogat et al 2007;Auf et al 2010Auf et al , 2013. Th is stress is recognized as an important determinant of cancer and contributes to the expression profi le of many regulatory genes resulting in proliferation, apoptosis, angiogenesis, and circadian clock (Clarke et al 2014;Manie et al 2014;Pluquet et al 2014;Dejeans et al 2015;Minchenko et al 2015). Th e IRE1 enzyme is responsible for degradation of a specifi c subset of mRNA and alternative splicing of the XBP1 (X-box binding protein 1) transcription factor mRNA for control of the expression of unfolded protein response-specifi c genes (Acosta-Alvear et al 2007;Aragon et al 2009;Dejeans et al 2012;Pluquet et al 2013;Maurel et al 2014Maurel et al , 2015.…”

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Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition

et al. 2017

Endocrine Regulations

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Objective. Th e aim of the present study was to examine the eff ect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoded estrogen related proteins (NRIP1/RIP140, TRIM16/EBBP, ESRRA/NR3B1, FAM162A/E2IG5, PGRMC2/PMBP, and SLC39A6/LIV-1) and their hypoxic regulation in U87 glioma cells for evaluation of their possible signifi cance in the control of glioma cells proliferation.Methods. Th e expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells, transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia, was studied by a quantitative polymerase chain reaction.Results. Inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 signaling enzyme function up-regulates the expression of EBBP, E2IG5, PGRMC2, and SLC39A6 genes is in U87 glioma cells in comparison with the control glioma cells, with more signifi cant changes for E2IG5 and PGRMC2 genes. At the same time, the expression of NRIP1 and ESRRA genes is strongly down-regulated in glioma cells upon inhibition of IRE1. We also showed that hypoxia increases the expression of E2IG5, PGRMC2, and EBBP genes and decreases NRIP1 and ESRRA genes expression in control glioma cells. Furthermore, the inhibition of IRE1 in U87 glioma cells decreases the eff ect of hypoxia on the expression of E2IG5 and PGRMC2 genes, eliminates hypoxic regulation of NRIP1 gene, and enhances the sensitivity of ESRRA gene to hypoxic condition. Furthermore, the expression of SLC39A6 gene is resistant to hypoxia in both the glioma cells with and without IRE1 signaling enzyme function. Conclusions.Results of this investigation demonstrate that inhibition of IRE1 signaling enzyme function aff ects the expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells in gene specifi c manner and these changes possibly contribute to the suppression of the cell proliferation. Most of these genes are regulated by hypoxia and preferentially through IRE1 signaling pathway of endoplasmic reticulum stress.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition

et al. 2017

Endocrine Regulations

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Nanoparticles for Targeting Intratumoral Hypoxia: Exploiting a Potential Weakness of Glioblastoma

et al. 2016

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Extensive hypoxic regions are the daunting hallmark of glioblastoma, as they host aggressive stem-like cells, hinder drug delivery and shield cancer cells from the effects of radiotherapy. Nanotechnology could address most of these issues, as it employs nanoparticles (NPs) carrying drugs that selectively accumulate and achieve controlled drug release in tumor tissues. Methods overcoming the stiff interstitium and scarce vascularity within hypoxic zones include the incorporation of collagenases to degrade the collagen-rich tumor extracellular matrix, the use of multistage systems that progressively reduce NP size or of NP-loaded cells that display inherent hypoxia-targeting abilities. The unfavorable hypoxia-induced low pH could be converted into a therapeutical advantage by pH-responsive NPs or multilayer NPs, while overexpressed markers of hypoxic cells could be specifically targeted for an enhanced preferential drug delivery. Finally, promising new gene therapeutics could also be incorporated into nanovehicles, which could lead to silencing of hypoxia-specific genes that are overexpressed in cancer cells. In this review, we highlight NPs which have shown promising results in targeting cancer hypoxia and we discuss their applicability in glioblastoma, as well as possible limitations. Novel research directions in this field are also considered.

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Exploring the Role of HtrA Family Genes in Cancer: A Systematic Review

Rosochowicz,

Kulcenty,

Suchorska

2024

Mol Diagn Ther

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Purpose HtrA1 , HtrA2 , HtrA3 and HtrA4 appear to be involved in the development of pathologies such as cancer. This systematic review reports the results of a literature search performed to compare the expression of HtrA family genes and proteins in cancer versus non-cancer tissues and cell lines, assess relationships between HtrA expression and cancer clinical features in cancer, and analyse the molecular mechanism, by which HtrA family affects cancer. Methods The literature search was conducted according to the PRISMA statement among four databases (PubMed, Web of Science, Embase and Scopus). Results A total of 38 articles met the inclusion criteria and involved the expression of HtrA family members and concerned the effect of HtrA expression on cancer and metastasis development or on the factor that influences it. Additionally, 31 reports were retrieved manually. Most articles highlighted that HtrA1 and HtrA3 exhibited tumour suppressor activity, while HtrA2 was associated with tumour growth and metastasis. There were too few studies to clearly define the role of the HtrA4 protease in tumours. Conclusion Although the expression of serine proteases of the HtrA family was dependent on tumour type, stage and the presence of metastases, most articles indicated that HtrA1 and HtrA3 expression in tumours was downregulated compared with healthy tissue or cell lines. The expression of HtrA2 was completely study dependent. The limited number of studies on HtrA4 expression made it impossible to draw conclusions about differences in expression between healthy and tumour tissue. The conclusions drawn from the study suggest that HtrA1 and HtrA3 act as tumour suppressors. Supplementary Information The online version contains supplementary material available at 10.1007/s40291-024-00712-2.

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Expression of insulin-like growth factor binding protein genes and its hypoxic regulation in U87 glioma cells depends on ERN1 mediated signaling pathway of endoplasmic reticulum stress

Cited by 33 publications

References 0 publications

Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition

Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition

Nanoparticles for Targeting Intratumoral Hypoxia: Exploiting a Potential Weakness of Glioblastoma

Exploring the Role of HtrA Family Genes in Cancer: A Systematic Review

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