<scp>INPP</scp>4B restrains cell proliferation and metastasis via regulation of the <scp>PI</scp>3K/<scp>AKT</scp>/<scp>SGK</scp> pathway

Chen, Ying; Sun, Z.G.; Qi, Mei; Wang, Xiao; Zhang, Weifang; Chen, Chunyan; Liu, Juan; Zhao, Weiming

doi:10.1111/jcmm.13595

Cited by 36 publications

(28 citation statements)

References 28 publications

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“…Thus, up-regulation of the expression of these multifunctional kinases (SGK1 and SGK3) in glioma cells under glucose deprivation conforms well to pro-proliferative role of these proteins. At the same time, inhibition of ERN1 signaling enzyme function has strong but different effect on their expression indicating ERN1 dependent character of these gene expressions and variable role in ERN1 signaling (Chen et al 2018;Li et al 2018b;Cao et al 2019;Fan et al 2019;Ma et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Effect of glucose deprivation on the expression of genes encoding glucocorticoid receptor and some related factors in ERN1-knockdown U87 glioma cells

Riabovol

Tsymbal

Minchenko

et al. 2019

Endocrine Regulations

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Objective. The aim of the present study was to examine the effect of glucose deprivation on the expression of genes encoded glucocorticoid receptor (NR3C1) and some related proteins (NR3C2, AHR, NRIP1, NNT, ARHGAP35, SGK1, and SGK3) in U87 glioma cells in response to inhibition of endoplasmic reticulum stress signaling mediated by ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1/inositol requiring enzyme 1) for evaluation of their possible significance in the control of glioma growth through endoplasmic reticulum stress signaling mediated by IRE1 and glucose deprivation.Methods. The expression of NR3C1, NR3C2, AHR, NRIP1, NNT, ARHGAP35, SGK1, and SGK3 genes in U87 glioma cells transfected by empty vector pcDNA3.1 (control cells) and cells without ERN1 signaling enzyme function (transfected by dnERN1) under glucose deprivation was studied by real time quantitative polymerase chain reaction.Results. It was shown that the expression level of NR3C2, AHR, SGK1, SGK3, and NNT genes was up-regulated in control U87 glioma cells under glucose deprivation condition in comparison with the control cells growing with glucose. At the same time, the expression of NRIP1 gene is down-regulated in these glioma cells under glucose deprivation, but NR3C1 and ARHGAP35 genes was resistant to this experimental condition. We also showed that inhibition of ERN1 signaling enzyme function significantly modified the response of most studied gene expressions to glucose deprivation condition. Thus, effect of glucose deprivation on the expression level of NR3C2, AHR, and SGK1 genes was significantly stronger in ERN1 knockdown U87 glioma cells since the expression of NNT gene was resistant to glucose deprivation condition. Moreover, the inhibition of ERN1 enzymatic activities in U87 glioma cells led to up-regulation of ARHGAP35 gene expression and significant down-regulation of the expression of SGK3 gene in response to glucose deprivation condition.Conclusions. Results of this study demonstrated that glucose deprivation did not change the expression level of NR3C1 gene but it significantly affected the expression of NR3C2, AHR, NRIP, SGK1, SGK3, and NNT genes in vector-transfected U87 glioma cells in gene specific manner and possibly contributed to the control of glioma growth since the expression of most studied genes in glucose deprivation condition was significantly dependent on the functional activity of IRE1 signaling enzyme.

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Section: Discussionmentioning

confidence: 99%

Effect of glucose deprivation on the expression of genes encoding glucocorticoid receptor and some related factors in ERN1-knockdown U87 glioma cells

Riabovol

Tsymbal

Minchenko

et al. 2019

Endocrine Regulations

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“…7 The INPP4B gene harbors a series of special structures, such as a C2 lipid binding domain at the N-terminal that promotes the dephosphorylation and degradation of phosphatidylinositol-3,4 diphosphate, thereby inhibiting AKT activation, blocking PI3K/AKT signaling pathway transmission, and inhibiting tumor progression. 8 The PTEN gene, as the first cancer suppressor gene with bispecific phosphatase activity is widely expressed in normal tissues. 9 PTEN protein converts 3,4,5-phosphatidylinositol into 4,5-phosphatidylinositol, induces Caspase-9 protein expression, and mediates cancer cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

The expression of PTEN and INPP4B and their clinical significance in patients with acute myeloid leukemia

et al. 2019

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This study investigates the expression of phosphatase and tensin homolog (PTEN) and Inositol polyphosphate 4-phosphatase type II (INPP4B) in children with acute myeloid leukemia. The levels of PTEN and INPP4B in bone marrow, from 95 acute myelogenous leukemia (AML) patients and 84 controls, respectively, were assessed by immunohistochemistry, quantitative polymerase chain reaction (qPCR), and Western blot. The prognosis was followed up and investigated and the correlation analysis was made. We found that the expression levels of PTEN and INPP4B were significantly lower in the AML group than those in the control group (P < 0.05). The survival time was lower in PTEN and INPP4B negative children relative to PTEN and INPP4B positive children (P < 0.05). In AML patients, INPP4B and PTEN expression was positively correlated (r = 0.552, P = 0.000). In conclusion, the levels of INPP4B and PTEN were reduced significantly and correlated positively in AML patients accompanying with abnormal karyotypes. The current investigation of INPP4B and PTEN could give new insight into targeted therapy for AML.

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“…Since SGK3 was a target gene regulated by miR-335-5p, and it was shown to affect the cell proliferation in many types of cells (Sun et al 2016, Chen et al 2018, we hypothesized that miR-335-5p might be associated with the growth and proliferation in granulosa cells. assay revealed that the miR-335-5p mimics significantly decreased cell proliferation, whereas the miR-335-5p inhibitor promoted the proliferation of KGN cells ( Fig.…”

Section: Mir-335-5p Inhibited Kgn Cells Proliferationmentioning

confidence: 99%

miRNA-335-5p negatively regulates granulosa cell proliferation via SGK3 in PCOS

Yao

et al. 2018

Reproduction

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Polycystic ovary syndrome (PCOS) is a major cause of infertility in women of reproductive age. However, its exact etiology remains unknown. In this study, we sequenced miRNAs in human follicular fluid and identified 16 downregulated and 3 upregulated miRNAs in PCOS group compared with non-PCOS group. Among the differential expressed miRNAs, miR-335-5p was verified lower abundance in PCOS than non-PCOS group using quantitative real-time PCR. Besides, miR-335-5p negatively correlated with antral follicle count, anti-Müllerian hormone and total testosterone. Bioinformatics analysis identified serum/glucocorticoid-regulated kinase family member 3 (SGK3) as a potential target gene of miR-335-5p. SGK3 is involved in protein kinase B-mammalian target of rapamycin kinase (AKT-mTOR) signaling pathway and cell proliferation. Western blotting and cell counting kit-8 assays demonstrated that miR-335-5p mimic reduced, while miR-335-5p inhibitor increased, SGK3 abundance, AKT-mTOR pathway and cell proliferation in human granulosa-like tumor KGN cells. Dual-luciferase reporter assays showed that miR-335-5p binds to the 3′ untranslated region of SGK3 mRNA. Furthermore, miR-335-5p was decreased and SGK3 was elevated in human granulosa cells obtained from PCOS patients as compared with non-PCOS controls. These findings suggested that miR-335-5p is involved in granulosa cells proliferation by reducing SGK3 expression, which might provide a molecular target to improve dysfunctional granulosa cells in patients with PCOS.

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INPP4B restrains cell proliferation and metastasis via regulation of the PI3K/AKT/SGK pathway

Cited by 36 publications

References 28 publications

Effect of glucose deprivation on the expression of genes encoding glucocorticoid receptor and some related factors in ERN1-knockdown U87 glioma cells

Effect of glucose deprivation on the expression of genes encoding glucocorticoid receptor and some related factors in ERN1-knockdown U87 glioma cells

The expression of PTEN and INPP4B and their clinical significance in patients with acute myeloid leukemia

miRNA-335-5p negatively regulates granulosa cell proliferation via SGK3 in PCOS

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