Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis

Machado-Neto, João Agostinho; Fenerich, Bruna Alves; Alves, Ana Paula Nunes Rodrigues; Fernandes, Janainny Magalhães; Scopim-Ribeiro, Renata; Coelho-Silva, Juan Luiz; Traina, Fabı́ola

doi:10.6061/clinics/2018/e566s

Cited by 36 publications

(19 citation statements)

References 118 publications

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“…As shown in Figure 3, IRS1 overexpression significantly increased the viability of U-87 MG cells. Previous studies have shown the role of IRS1 in cell proliferation and viability [9,14,17].…”

Section: Discussionmentioning

confidence: 96%

Insulin receptor substrate 1 overexpression promotes survival of glioblastoma cells through AKT1 activation

Görgişen¹,

Yaren²

2020

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Glioblastoma multiforme (GBM) is the most common and malignant type of central nervous system tumours in adults. Strict regulation of glucose homeostasis has a significant role in GBM pathogenesis. Insulin receptor substrate 1 (IRS1) protein is the most important adaptor molecule involved in the regulation of glucose metabolism. It interacts with many cancer-related receptors and its overexpression is strongly associated with cell proliferation and survival. Our study was aimed to understand the role of IRS1 proteins in GBM cell viability. U-87 MG cells were transfected with pcDNA3.1-flagtagged-human IRS1 expression vector. Insulin induced phosphorylation levels of IRS1, AKT1 and ERK1/2 and Grb2 expression were examined to determine the effects of ectopic IRS1 overexpression on insulin signalling and the viability levels of U-87 MG cells were determined by MTT analysis. Overexpression of IRS1 in U-87 MG cells led to an increase in cell viability. Its overexpression also increased Grb2 expression and phosphorylation of AKT1 through elevation of IRS1 tyrosine phosphorylation in IRS1-transfected U-87 MG cells compared to control and mock transfected groups. Our study showed that increased IRS1 expression and activation may promote the cell viability via AKT1 activation. IRS1 signalling may be considered as a therapeutic target for further studies.

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Section: Discussionmentioning

confidence: 96%

Insulin receptor substrate 1 overexpression promotes survival of glioblastoma cells through AKT1 activation

Görgişen¹,

Yaren²

2020

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“…Phosphorylated INSR and IGF1R are also involved in the regulation of cell proliferation, differentiation, and survival. The IRS family includes four isoforms, IRS1-4 (Al-Salam and Irwin 2017;Machado-Neto et al 2018). IRS1 is a mediator of insulin and IGF1, both of which can bind to INSR (Simpson et al 2017;Frezza et al 2018).…”

Section: Discussionmentioning

confidence: 99%

“…The IRS family includes four isoforms, IRS1-4 (Al-Salam and Irwin 2017 ; Machado-Neto et al. 2018 ). IRS1 is a mediator of insulin and IGF1, both of which can bind to INSR (Simpson et al.…”

Section: Discussionmentioning

confidence: 99%

Effects of Heshouwuyin on gene expression of the insulin/IGF signalling pathway in rat testis and spermatogenic cells

Wang

Shan

Duan

et al. 2020

Pharmaceutical Biology

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Context: The Chinese herbal formula Heshouwu decoction (Heshouwuyin) has protective effects on testicular function in aging male rats, but the mechanism is unknown. Objective: This study investigated whether Heshouwuyin affects the testicular function of aging rats by regulating the insulin/IGF signalling pathway. Materials and methods: Sixteen-month-old male Wistar rats in the Heshouwuyin group and the naturalaging group were orally administered Heshouwuyin granules (0.056 g/kg) or equivalent normal saline for 60 d. The testicular tissue of 12-month-old male Wistar rats was removed as a young control group (n ¼ 10). The testicular tissue and spermatogenic cells were studied. Results: The immunofluorescence results revealed that the insulin receptor (INSR)-(0.056 ± 0.00548), insulin receptor substrate 1(IRS1)-(0.251 ± 0.031), IRS2 (0.230 ± 0.019)-and insulin-like growth factor 1 (IGF1)positive cell rate (0.33 ± 0.04) in the aging group was higher than that in the young control group (0.116 ± 0.011, 0.401 ± 0.0256, 0.427 ± 0.031, 0.56 ± 0.031; p < 0.01), and the IGF-binding protein 3 (IGFBP3)positive cell rate (0.42 ± 0.024) was lower than that (0.06 ± 0.027) in the young group (p < 0.01). The intervention of Heshouwuyin reversed the above phenomena. The qPCR and immunoblot results were consistent with those of the immunofluorescence. The same results were obtained in spermatogenic cells. Conclusions: Our research shows that Heshouwuyin can regulate the insulin/IGF signalling pathway to improve testicular function, and provides an experimental basis for further clinical use.

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“…IRS is known as cytoplasmic protein that integrates and coordinates signals from the extracellular to the intracellular environment through transmembrane receptors, which plays a crucial role in regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/MTOR and MAPK signaling pathways are the most typical downstream signaling pathways for IRS signal activation [40]. As an important member of IRS family, IRS2 is involved in the promotion of malignant progression in multiple tumors, such and NSCLC [20,22,41].In addition, IRS2 is validated to be regulated by miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Circ_0000003 promotes the proliferation and metastasis of non-small cell lung cancer cells via miR-338-3p/insulin receptor substrate 2

Niu

et al. 2019

Cell Cycle

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Background: Circular RNAs (circRNAs) play a pivotal regulatory role in a variety of tumors. Nevertheless, the detailed function of circ_0000003 in non-small cell lung cancer (NSCLC) and its regulatory mechanism remain elusive. Methods: RT-PCR was carried out to detect the expressions of circ_0000003, miR-338-3p and insulin receptor substrate 2 (IRS2)in NSCLC tissues. Besides, western blot was done to monitor IRS2 expression in NSCLC cells. The correlation between circ_0000003 and clinicopathologic characteristics of NSCLC patients was analyzed as well.CCK8 and BrdUassays were used to monitor cell proliferation; flow cytometry was used to detect apoptosis; and transwell assay was conducted to detect its migration and invasion.Moreover, dual luciferase reporter gene assay was done to verify the targeting relationship between circ_0000003 and miR-338-3p.Additionally, the effect of circ_0000003 on the growth of NSCLC cells in vivo was evaluated by tumorigenesis assay in nude mice. Results: The expression of circ_0000003 was significantly high in NSCLC tissues and cell lines, and its high expression level was notably correlated with lymph node metastasis andTNM staging.In vitro experiments showed that overexpression of circ_0000003 facilitated the proliferation, migration, invasion and inhibited the apoptosis of NSCLC cells, while the knockdown of circ_0000003 had the opposite effect.In vivo experiments revealed that knockdown of circ_0000003 impeded tumor growth and metastasis. Further, the underlying mechanism showed that circ_0000003 functioned as endogenous competitive RNA and directly targeted miR-338-3p to positively regulated IRS2 expression. Conclusion: Circ_0000003 promotes the proliferation and metastasis of NSCLC cells via modulating miR-338-3p/IRS2 axis.

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Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis

Cited by 36 publications

References 118 publications

Insulin receptor substrate 1 overexpression promotes survival of glioblastoma cells through AKT1 activation

Insulin receptor substrate 1 overexpression promotes survival of glioblastoma cells through AKT1 activation

Effects of Heshouwuyin on gene expression of the insulin/IGF signalling pathway in rat testis and spermatogenic cells

Circ_0000003 promotes the proliferation and metastasis of non-small cell lung cancer cells via miR-338-3p/insulin receptor substrate 2

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