scholarly journals Molecular mechanism of the “feedback loop” model of carcinogenesis

2012 ◽  
Vol 5 (5) ◽  
pp. 506-507
Author(s):  
Felix Rückert ◽  
Carsten Sticht ◽  
Marco Niedergethmann
Keyword(s):  
Molecular Mechanism ◽  
Feedback Loop ◽  
Loop Model

scholarly journals Molecular Mechanism of Cell-autonomous Circadian Gene Expression of Period2, a Crucial Regulator of the Mammalian Circadian Clock

2006 ◽  
Vol 17 (2) ◽  
pp. 555-565 ◽  
Author(s):  
Makoto Akashi ◽  
Tomoko Ichise ◽  
Takayoshi Mamine ◽  
Toru Takumi
Keyword(s):  
Gene Expression ◽  
Molecular Mechanism ◽  
Feedback Loop ◽  
Basic Mechanism ◽  
Loop Model ◽  
Circadian Gene ◽  
Current Feedback ◽  
E Box ◽  
Transcriptional Elements ◽  
Circadian Transcription

Although circadian transcription of Period2 (Per2) is fundamental for the generation of circadian rhythm, the molecular mechanism remains unclear. Here we report that cell-autonomous circadian transcription of Per2 is driven by two transcriptional elements, one for rhythm generation and the other for phase control. The former contains the E-box-like sequence (CACGTT) that is sufficient and indispensable to drive oscillation, and indeed circadian transcription factors site-specifically bind to it. Furthermore, the nature of this atypical E-box is different from that of the classical circadian E-box. The current feedback loop model is based mainly on Period1. Our results provide not only compelling evidence in support of this model but also an explanation for a general basic mechanism to produce various patterns in the phase and amplitude of cell-autonomous circadian gene expression.

scholarly journals miR-29a sensitizes the response of glioma cells to temozolomide by modulating the P53/MDM2 feedback loop

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Qiudan Chen ◽  
Weifeng Wang ◽  
Shuying Chen ◽  
Xiaotong Chen ◽  
Yong Lin
Keyword(s):  
Molecular Mechanism ◽  
Feedback Loop ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Aberrant Expression ◽  
Altered Expression ◽  
P53 Signaling

AbstractRecently, pivotal functions of miRNAs in regulating common tumorigenic processes and manipulating signaling pathways in brain tumors have been recognized; notably, miR‐29a is closely associated with p53 signaling, contributing to the development of glioma. However, the molecular mechanism of the interaction between miR-29a and p53 signaling is still to be revealed. Herein, a total of 30 glioma tissues and 10 non-cancerous tissues were used to investigate the expression of miR‐29a. CCK-8 assay and Transwell assay were applied to identify the effects of miR-29a altered expression on the malignant biological behaviors of glioma cells in vitro, including proliferation, apoptosis, migration and invasion. A dual-luciferase reporter assay was used to further validate the regulatory effect of p53 or miR-29a on miR-29a or MDM2, respectively, at the transcriptional level. The results showed that miR-29a expression negatively correlated with tumor grade of human gliomas; at the same time it inhibited cell proliferation, migration, and invasion and promoted apoptosis of glioma cells in vitro. Mechanistically, miR-29a expression was induced by p53, leading to aberrant expression of MDM2 targeted by miR-29a, and finally imbalanced the activity of the p53-miR-29a-MDM2 feedback loop. Moreover, miR-29a regulating p53/MDM2 signaling sensitized the response of glioma cells to temozolomide treatment. Altogether, the study demonstrated a potential molecular mechanism in the tumorigenesis of glioma, while offering a possible target for treating human glioma in the future.

scholarly journals Feedback loop and upwind-propagating waves in ideally expanded supersonic impinging round jets

2017 ◽  
Vol 823 ◽  
pp. 562-591 ◽  
Author(s):  
Christophe Bogey ◽  
Romain Gojon
Keyword(s):  
Flat Plate ◽  
Acoustic Waves ◽  
Feedback Loop ◽  
Supersonic Jet ◽  
Vortex Sheet ◽  
Impinging Jets ◽  
Loop Model ◽  
Turbulent Structures ◽  
Fourier Decomposition ◽  
Pressure Fields

The aeroacoustic feedback loop establishing in a supersonic round jet impinging on a flat plate normally has been investigated by combining compressible large-eddy simulations and modelling of that loop. At the exit of a straight pipe nozzle of radius $r_{0}$, the jet is ideally expanded, and has a Mach number of 1.5 and a Reynolds number of $6\times 10^{4}$. Four distances between the nozzle exit and the flat plate, equal to $6r_{0}$, $8r_{0}$, $10r_{0}$ and $12r_{0}$, have been considered. In this way, the variations of the convection velocity of the shear-layer turbulent structures according to the nozzle-to-plate distance are shown. In the spectra obtained inside and outside of the flow near the nozzle, several tones emerge at Strouhal numbers in agreement with measurements in the literature. At these frequencies, by applying Fourier decomposition to the pressure fields, hydrodynamic-acoustic standing waves containing a whole number of cells between the nozzle and the plate and axisymmetric or helical jet oscillations are found. The tone frequencies and the mode numbers inferred from the standing-wave patterns are in line with the classical feedback-loop model, in which the loop is closed by acoustic waves outside the jet. The axisymmetric or helical nature of the jet oscillations at the tone frequencies is also consistent with a wave analysis using a jet vortex-sheet model, providing the allowable frequency ranges for the upstream-propagating acoustic wave modes of the jet. In particular, the tones are located on the part of the dispersion relations of the modes where these waves have phase and group velocities close to the ambient speed of sound. Based on the observation of the pressure fields and on frequency–wavenumber spectra on the jet axis and in the shear layers, such waves are identified inside the present jets, for the first time to the best of our knowledge, for a supersonic jet flow. This study thus suggests that the feedback loop in ideally expanded impinging jets is completed by these waves.

Flux module decomposition for parameter estimation in a multiple-feedback loop model of biochemical networks

2012 ◽  
Vol 36 (3) ◽  
pp. 333-344 ◽  
Author(s):  
Kazuhiro Maeda ◽  
Hiroshi Minamida ◽  
Keisuke Yoshida ◽  
Hiroyuki Kurata
Keyword(s):  
Parameter Estimation ◽  
Feedback Loop ◽  
Biochemical Networks ◽  
Loop Model

scholarly journals A dual-feedback loop model of the mammalian circadian clock for multi-input control of circadian phase

2020 ◽  
Vol 16 (11) ◽  
pp. e1008459
Author(s):  
Lindsey S. Brown ◽  
Francis J. Doyle
Keyword(s):  
Circadian Clock ◽  
Small Molecules ◽  
Feedback Loop ◽  
Feedback Loops ◽  
The Body ◽  
Loop Model ◽  
Circadian Phase ◽  
Input Control ◽  
Cellular Components

The molecular circadian clock is driven by interlocked transcriptional-translational feedback loops, producing oscillations in the expressions of genes and proteins to coordinate the timing of biological processes throughout the body. Modeling this system gives insight into the underlying processes driving oscillations in an activator-repressor architecture and allows us to make predictions about how to manipulate these oscillations. The knockdown or upregulation of different cellular components using small molecules can disrupt these rhythms, causing a phase shift, and we aim to determine the dosing of such molecules with a model-based control strategy. Mathematical models allow us to predict the phase response of the circadian clock to these interventions and time them appropriately but only if the model has enough physiological detail to describe these responses while maintaining enough simplicity for online optimization. We build a control-relevant, physiologically-based model of the two main feedback loops of the mammalian molecular clock, which provides sufficient detail to consider multi-input control. Our model captures experimentally observed peak to trough ratios, relative abundances, and phase differences in the model species, and we independently validate this model by showing that the in silico model reproduces much of the behavior that is observed in vitro under genetic knockout conditions. Because our model produces valid phase responses, it can be used in a model predictive control algorithm to determine inputs to shift phase. Our model allows us to consider multi-input control through small molecules that act on both feedback loops, and we find that changes to the parameters of the negative feedback loop are much stronger inputs for shifting phase. The strongest inputs predicted by this model provide targets for new experimental small molecules and suggest that the function of the positive feedback loop is to stabilize the oscillations while linking the circadian system to other clock-controlled processes.

scholarly journals C-MYC inducible onco-lncRNA LINC00036 acting as EGFR mRNA stabilizer via RNA-protein and RNA-RNA interactions decreases the sensitivity of gefitinib in human cancer

2021 ◽  
Author(s):  
Shouping Xu ◽  
Lin Wan ◽  
Qin Wang ◽  
Huizi Yin ◽  
Kun Qiao ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Molecular Mechanism ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Positive Feedback Loop ◽  
Different Types

Abstract Background: The oncogenic lncRNA based strategies for combating cancer may usher in a new and promising paradigm in cancer therapy. However, few studies have been performed to solve such a critical issue. The complex traits and molecular mechanism of such lncRNAs in tumorigenesis and their relationship with sensitivity of gefitinib in human cancer have not been investigated.Methods: We aimed to identify and validate such a novel oncogenic LINC00036 using transcriptome sequencing approach and a large number of tissue samples of different types of cancer from the our cancer center cohort and public data cohorts from the Cancer Genome Atlas，Gene Expression Omnibus and Cancer Cell Line Encyclopedia. Moreover, series of in vitro and in vivo experiments were performed to examine its roles in tumorigenesis and the sensitivity of gefitinib in different types of cancer cells. Special nanoparticle via a more potent delivery system was developed to investigate the feasibility of targeting LINC00036 in vivo. Furthermore, chromatin immunoprecipitation (ChIP)-sequencing, ChIP, actinomycin D assay, dual-luciferase reporter assay, RNA pull-down and RNA immunoprecipitation were performed were developed to uncover the molecular mechanism.Results: LINC00036 that associated with poor prognosis is significantly upregulated in human cancer tissues. Series of in vitro and in vivo experiments reveal that LINC00036 promotes tumorigenesis and decreases the sensitivity of gefitinib in different types of cancer cells. LINC00036 targeting nanoparticle markedly reduced the growth of human cancer xenografts. Mechanistically, LINC00036 is a direct transcriptional target of c-MYC and a positive feedback loop of the c-MYC-LINC00036-EGFR axis exists in human cancer. LINC00036 acts as an EGFR mRNA stabilizer via RNA-protein and RNA-RNA interactions, inducing the hyper-activation of the downstream AKT and MAPK signaling pathways, which in turn decreases the sensitivity of gefitinib in human cancer.Conclusions: LINC00036, a c-MYC inducible onco-lncRNA, acts an oncogene in human cancer and decreases the sensitivity of gefitinib through positive feedback loop of the c-MYC-LINC00036-EGFR axis. Overall, this study broadens knowledge regarding novel onco-lncRNAs and will assist in developing feasible onco-lncRNAs based-targeted therapeutic strategies to improve the sensitivity of gefitinib in human cancer.

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