The Role of miRNAs in PI3K Signaling Pathway in Blood Malignancies: A Review Article

2021 ◽  
Author(s):  
Haniyeh Gaffari-Nazari ◽  
Samira Karami ◽  
Leila Noorazar ◽  
Sayeh Parkhideh ◽  
Elham Roshandel ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Pi3k Pathway ◽  
Pi3k Signaling ◽  
Laboratory Findings ◽  
A Cell ◽  
Pi3k Signaling Pathway ◽  
Relationship Of

Background: The PI3K/Akt/mTOR signaling pathway is one of the most important intracellular signaling pathways by regulating the cell cycle process. The direct relationship of this pathway with important mechanisms such as cell quiescence, longevity, and proliferation has been established. The overactive PI3K pathway with decreased and increased apoptosis and cell proliferation respectively is involved in pathogenesis of many cancers, including blood malignancies such as leukemia. Methods: Laboratory findings have shown that different factors, such as miRNAs, play a role in regulating PI3K signaling pathway. These molecules can alter the fate of a cell by interfering in suppression/overexpression of mRNA, transcription factors or stimulating the transcription of some genes. In this article, we reviewed the role of miRNAs in regulating the PI3K/Akt/mTOR pathway and its effect on leukemic progression and treatment failure. Conclusion: At present, miRNAs are known to be one of the causes of treatment failure and relapse in cancers.

scholarly journals The PI3K signaling pathway mediates the biological effects of leptin

2010 ◽  
Vol 54 (7) ◽  
pp. 591-602 ◽  
Author(s):  
Jose Donato Jr. ◽  
Renata Frazão ◽  
Carol Fuzeti Elias
Keyword(s):  
Food Intake ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Leptin Receptor ◽  
Biological Effects ◽  
Pi3k Pathway ◽  
Pi3k Signaling ◽  
Electrophysiological Properties ◽  
Pi3k Signaling Pathway

The activation of the leptin receptor recruits several intracellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3K) pathway. While some of the leptin-induced signaling pathways, such as the JAK2/STAT3 pathway, induce cellular responses primarily through changes in gene expression, the PI3K pathway affects cellular properties more rapidly, through post-translational changes such as protein phosphorylation. Accordingly, several studies have shown that the PI3K pathway is required for the acute effects of leptin, such as a leptin-induced decrease in food intake. Leptin signaling through PI3K also affects the electrophysiological properties of neurons, including changes in their membrane potential and firing rates. In this review, we summarize the recent advances in our understanding of the role played by the PI3K signaling pathway in controlling food intake and energy balance. In particular, we focus on the importance of the PI3K signaling pathway as a mediator of the effects of leptin on hypothalamic neurons.

scholarly journals BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells

2020 ◽  
Vol 15 (1) ◽  
pp. 501-510
Author(s):  
Bin Ma ◽  
Wenjia Guo ◽  
Meihui Shan ◽  
Nan Zhang ◽  
Binlin Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Nuclear Localization ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pi3k Pathway ◽  
Pi3k Signaling ◽  
T47d Cells ◽  
Pi3k Signaling Pathway ◽  
Hormone Sensitive

AbstractThis study is to investigate the effect of the PI3K/Akt signaling pathway on the regulation of BRCA1 subcellular localization in triple-negative breast cancer (TNBC) MDA-MB-231 cells and hormone-sensitive T47D cells. We found that heregulin-activated T47D cells showed more nuclear localization of BRCA1, but BRCA1 nuclear localization decreased after the inhibition of the PI3K signaling pathway. In MDA-MB-231 cells, activation or inhibition of the PI3K signaling pathway did not significantly affect cell apoptosis and BRCA1 nuclear translocation (P > 0.05). However, in T47D cells, the activation of the PI3K pathway significantly increased cell apoptosis (P < 0.05). In the heregulin-activated MDA-MB-231 and T47D cells, the phosphorylation of Akt and BRCA1 was significantly increased (P < 0.05), while that was significantly reduced after PI3K pathway inhibition (P < 0.05). The changing trends of the mRNA levels of Akt and BRCA1 in MDA-MB-231 and T47D cells after PI3K pathway activation or inhibition were consistent with the trends of their proteins. In both MDA-MB-231 and T47D cells, BRCA1 phosphorylation is regulated by the PI3K signaling pathway, but the nuclear localization of BRCA1 is different in these two cell lines. Moreover, the apoptosis rates of these two cell lines are different.

scholarly journals Short-term effects of triiodothyronine on thyroid hormone receptor alpha by PI3K pathway in adipocytes, 3T3-L1

2014 ◽  
Vol 58 (8) ◽  
pp. 833-837 ◽  
Author(s):  
Miriane de Oliveira ◽  
Regiane Marques Castro Olimpio ◽  
Maria Teresa De Sibio ◽  
Fernanda Cristina Fontes Moretto ◽  
Renata de Azevedo Mello Luvizotto ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Thyroid Hormone Receptor ◽  
Pi3k Pathway ◽  
Control Group ◽  
Pi3k Signaling ◽  
Pi3k Inhibitor Ly294002 ◽  
Receptor Alpha ◽  
Pi3k Signaling Pathway

Objective The present study aimed to examine the effects of thyroid hormone (TH), more precisely triiodothyronine (T3), on the modulation of TH receptor alpha (TRα) mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K) signaling pathway in adipocytes, 3T3-L1, cell culture. Materials and methods: It was examined the involvement of PI3K pathway in mediating T3 effects by treating 3T3-L1 adipocytes with physiological (P=10nM) or supraphysiological (SI =100 nM) T3 doses during one hour (short time), in the absence or the presence of PI3K inhibitor (LY294002). The absence of any treatment was considered the control group (C). RT-qPCR was used for mRNA expression analyzes. For data analyzes ANOVA complemented with Tukey’s test was used at 5% significance level. Results T3 increased TRα mRNA expression in P (1.91±0.13, p<0.001), SI (2.14±0.44, p<0.001) compared to C group (1±0.08). This increase was completely abrogated by LY294002 in P (0.53±0.03, p<0.001) and SI (0.31±0.03, p<0.001). To examine whether TRα is directly induced by T3, we used the translation inhibitor cycloheximide (CHX). The presence of CHX completely abrogated levels TRα mRNA in P (1.15±0.05, p>0.001) and SI (0.99±0.15, p>0.001), induced by T3. Conclusion These results demonstrate that the activation of the PI3K signaling pathway has a role in T3-mediated indirect TRα gene expression in 3T3-L1 adipocytes.

scholarly journals OR20-01 AMH Preserves Fertility in Chemotherapy-Treated Mice Through a Mechanism Involving Autophagy

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Isabelle Beau ◽  
Charlotte Sonigo ◽  
Nadine Binart
Keyword(s):  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Alkylating Agents ◽  
Phosphatidyl Inositol ◽  
Autophagic Flux ◽  
Pi3k Signaling ◽  
Primordial Follicles ◽  
Pi3k Signaling Pathway

Abstract Chemotherapy-induced ovarian failure and infertility is an important concern in female cancer patients. The follicular ovarian reserve is established early in life then keeps declining regularly along reproductive life. This reserve is constituted by dormant primordial follicles (PMF) which are necessary to maintain female reproductive function. There is a continuous repression of PMF activation in early growing follicle through the balance between factors activating the initiation of follicular growth, mainly actors of the phosphatidyl-inositol-3-kinase (PI3K) signaling pathway, and inhibiting factors such as Anti-Müllerian Hormone (AMH). Any alteration of this equilibrium may induce early follicle depletion and subsequent infertility. Cyclophosphamide (Cy) one of the alkylating agents commonly used for treating breast cancer is able to trigger PMF activation further leading to premature ovarian insufficiency. Preventing chemotherapy-induced ovarian dysfunction might represent an option for preserving optimal chances of natural or medically assisted conceptions after healing. We showed in a model of Cy-treated pubertal mice, that AMH administration was able to restrain PMF depletion by counting the total PMF number within mouse ovaries. Moreover, the PI3K signaling pathway was evaluated following Cy administration with and without AMH injection. We showed that AMH decreased the phosphorylation of FOXO3A, a transcription factor of PMF activation and induced its nuclear translocation. Altogether, the results support a protective role of AMH against Cy-induced follicular loss. To better understand AMH action in the ovary, we investigated the molecular mechanism to explain the protective effect of this hormone on the PMF pool. It has been reported that autophagy, a lysosomal degradative ubiquitous process implicated in cellular homeostasis, was involved in both ovarian follicular death and survival mostly by PI3K pathway (Gawriluk et al. Reproduction 2011 141, 759–765). We show in mice that Cy inhibits autophagy in the ovary while AMH induces autophagy. In vivo analysis of autophagic flux is currently in progress to dissect this process more finely. Interestingly, FOXO3A was shown to be related to autophagy activation. To investigate the role of FOXO3A in AMH-induced autophagy further, we analyzed mRNA and protein expression of autophagy-related genes controlled by FOXO3A, including BECLIN-1, ATG12, ULK1, BNIP3, GABARAP, and LC3B. These findings establish a close relationship between AMH and autophagy to protect PMF stockpile and to limit follicular depletion induced by Cy.

scholarly journals Quercetin Prevents Primordial Follicle Loss via Suppression of PI3K/Akt/Foxo3a Pathway Activation in Cyclophosphamide - Treated Mouse

2020 ◽  
Author(s):  
Jianghui Li ◽  
Hui Long ◽  
Yanyan Cong ◽  
Hongyuan Gao ◽  
Qifeng Lyu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Survival Rates ◽  
Primordial Follicle ◽  
Pi3k Pathway ◽  
Pi3k Signaling ◽  
Primordial Follicles ◽  
Pathway Activation ◽  
Pi3k Signaling Pathway ◽  
Induced Apoptosis ◽  
Immunohistochemistry Stain

Abstract Background: Chemotherapy improves survival rates but often causes some adverse effects associated with ovarian damage, characterized by a decreased of primordial follicle stockpiles. Recent studies reveal that chemotherapy may stimulate the PI3K signaling pathway, who has roles in manipulating the dormancy and activation of mammalian primordial follicles, resulting in accelerated primordial follicles activation followed by the loss of ovarian reserve. As an inhibitor of PI3K pathway, whether quercetin has protective properties against chemotherapy - induced follicle loss in mice is worth to be explored.Methods: The effects of quercetin on the mouse model of cyclophosphamide-induced ovarian dysfunction were investigated. Paraffin sections of mouse ovary were stained with hematoxylin and eosin for differential follicles count and TUNEL assay for apoptosis detection. Immunohistochemistry stain with ki67 and Foxo3a were used to evaluate the activation of primordial follicles. The function of PI3K signaling pathway were assessed via the western blot of ovary.Results: Quercetin cotreatment rescued the reduction number of dormant primordial follicles induced by cyclophosphamide. Moreover, analysis of the PI3K/Akt/Foxo3a pathway demonstrated that quercetin co - administration decreased phosphorylation of proteins that stimulate follicle activation in ovary induced by cyclophosphamide. Meanwhile, Quercetin prevents cyclophosphamide - induced apoptosis in early growing follicles and early antral follicles, maintaining AMH level secreted by these follicles, preserving the quiescence of the primordial follicle pool, characterized by the intranuclear staining of Foxo3a in primordial follicle. Conclusions: Quercetin attenuates cyclophosphamide - induced follicle loss by preventing the phosphorylation of PI3K/Akt/Foxo3a pathway members and maintaining AMH level secreted by growing follicles.

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