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

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

“…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).…”

“…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).…”

“…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.…”

“…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).…”

“…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.…”