scholarly journals Double-negative feedback loop between MicroRNA-422a and forkhead box (FOX)G1/Q1/E1 regulates hepatocellular carcinoma tumor growth and metastasis

Hepatology ◽  
2015 ◽  
Vol 61 (2) ◽  
pp. 561-573 ◽  
Author(s):  
Jin Zhang ◽  
Yun Yang ◽  
Tian Yang ◽  
Shengxian Yuan ◽  
Ruoyu Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Double Negative ◽  
Forkhead Box ◽  
Tumor Growth And Metastasis ◽  
Carcinoma Tumor

scholarly journals A GYS2/p53 Negative Feedback Loop Restricts Tumor Growth in HBV-Related Hepatocellular Carcinoma

2018 ◽  
Vol 79 (3) ◽  
pp. 534-545 ◽  
Author(s):  
Shi-Lu Chen ◽  
Chris Zhiyi Zhang ◽  
Li-Li Liu ◽  
Shi-Xun Lu ◽  
Ying-Hua Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop

scholarly journals A double-negative feedback loop between EZH2 and miR-26a regulates tumor cell growth in hepatocellular carcinoma

2016 ◽  
Vol 48 (3) ◽  
pp. 1195-1204 ◽  
Author(s):  
CHUNBO ZHUANG ◽  
PEI WANG ◽  
DA HUANG ◽  
LUMING XU ◽  
XIAOBEI WANG ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Tumor Cell ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Double Negative ◽  
Tumor Cell Growth

scholarly journals The p53/miR-193a/EGFR feedback loop function as a driving force for non-small cell lung carcinoma tumorigenesis

2019 ◽  
Vol 11 ◽  
pp. 175883591985066 ◽  
Author(s):  
Wei Wang ◽  
Xia-Bo Shen ◽  
Wei Jia ◽  
Da-Bing Huang ◽  
Yong Wang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Lung Carcinoma ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Negative Feedback Loop ◽  
Double Negative ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Background: Non-small cell lung carcinoma (NSCLC) is a major worldwide health threat due to its low cure rate and high lethality. Emerging evidence suggests that epidermal growth factor receptor (EGFR) plays vital roles in cancer initiation and progression, and is considered an important cancer-driving protein. However, how EGFR expression is regulated during NSCLC development remains to be fully elucidated. Methods: In NSCLC clinical samples, EGFR protein levels were measured by western blotting and qRT-PCR, respectively. Combining microRNA (miRNA) target prediction software and the pulldown assay, we predicted microRNAs (miRNAs) that targeted EGFR. Next, three NSCLC cell lines, A549 (p53 WT), H322 (p53 mutant), and H1299 (p53 null), were used to demonstrate the direct targeting of EGFR by miR-193a. In addition, we investigated the biological effects of EGFR inhibition by miR-193a in vitro using Cell Counting Kit-8, 5-Ethynyl-2′-deoxyuridine (EdU), transwell, and apoptosis assays. Then, using ChIP and luciferase assays, we demonstrated that miR-193a was directly activated by p53 at the transcriptional level and that p53-induced-miR-193a and EGFR form a double-negative feedback loop. Results: We found that EGFR mRNA and protein were upregulated in NSCLC. We predicted that EGFR was a target of miR-193a and validated that miR-193a bound directly to the 3′-UTR of the EGFR mRNA. Moreover, miR-193a inhibited NSCLC proliferation and invasion, and promotes NSCLC apoptosis by directly downregulating EGFR. Then, we demonstrated that p53 directly activated miR-193a transcription, whereas EGFR functioned as a transcriptional repressor to negatively control miR-193a expression, forming a feedback loop. The loop promoted NSCLC cell proliferation and migration and accelerated tumor growth in xenograft mice. Conclusions: This study highlights a double-negative feedback loop in NSCLC. The feedback loop is crucial because overexpressing EGFR strongly accelerated tumor growth, while miR-193a restoration blocked tumor growth in vivo. Our findings are in line with the emerging opinion that miRNAs and protein regulators form regulatory networks in critical biological processes and that their dysregulation can lead to cellular dysfunction. In conclusion, this study provides important insights into the molecular mechanisms of NSCLC progression and may help inform the development of new therapeutics for managing NSCLC.

scholarly journals HIC1 and miR-23~27~24 clusters form a double-negative feedback loop in breast cancer

2016 ◽  
Vol 24 (3) ◽  
pp. 421-432 ◽  
Author(s):  
Yanbo Wang ◽  
Hongwei Liang ◽  
Geyu Zhou ◽  
Xiuting Hu ◽  
Zhengya Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Double Negative

scholarly journals Multistability and consequent phenotypic plasticity in AMPK-Akt double negative feedback loop in cancer cells

2020 ◽  
Author(s):  
Adithya Chedere ◽  
Kishore Hari ◽  
Saurav Kumar ◽  
Annapoorni Rangarajan ◽  
Mohit Kumar Jolly
Keyword(s):  
Breast Cancer ◽  
Phenotypic Plasticity ◽  
Cancer Cells ◽  
Cell Population ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Phenotypic Switching ◽  
Negative Feedback Loop ◽  
Double Negative ◽  
Protein Levels

AbstractAdaptation and survival of cancer cells to various stress and growth factor conditions is crucial for successful metastasis. A double-negative feedback loop between two serine/threonine kinases AMPK and Akt can regulate the adaptation of breast cancer cells to matrix-deprivation stress. This feedback loop can generate majorly two phenotypes or cell states: matrix detachment-triggered pAMPKhigh/ pAktlow state, and matrix (re)attachment-triggered pAkthigh/ pAMPKlow state. However, whether these two cell states can exhibit phenotypic plasticity and heterogeneity in a given cell population, i.e., whether they can co-exist and undergo spontaneous switching to generate the other subpopulation, remains unclear. Here, we develop a mechanism-based mathematical model that captures the set of experimentally reported interactions among AMPK and Akt. Our simulations suggest that the AMPK-Akt feedback loop can give rise to two co-existing phenotypes (pAkthigh/ pAMPKlow and pAMPKhigh/pAktlow) in specific parameter regimes. Next, to test the model predictions, we segregated these two subpopulations in MDA-MB-231 cells and observed that each of them was capable of switching to another in adherent conditions. Finally, the predicted trends are supported by clinical data analysis of TCGA breast cancer and pan-cancer cohorts that revealed negatively correlated pAMPK and pAkt protein levels. Overall, our integrated computational-experimental approach unravels that AMPK-Akt feedback loop can generate multistability and drive phenotypic switching and heterogeneity in a cancer cell population.

scholarly journals KLF2 inhibits TGF-β-mediated cancer cell motility in hepatocellular carcinoma

2020 ◽  
Vol 52 (5) ◽  
pp. 485-494 ◽  
Author(s):  
Yining Li ◽  
Shuo Tu ◽  
Yi Zeng ◽  
Cheng Zhang ◽  
Tian Deng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Motility ◽  
Cancer Cell ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Negative Feedback Loop ◽  
Liver Malignancy ◽  
Cancer Cell Motility

Abstract Feedback regulation plays a pivotal role in determining the intensity and duration of TGF-β signaling and subsequently affecting the pathophysiological roles of TGF-β, including those in liver malignancy. KLF2, a member of the Krüppel-like factor (KLF) family transcription factors, has been implicated in impeding hepatocellular carcinoma (HCC) development. However, the underlying molecular mechanisms are not fully understood. In the present study, we found that TGF-β stimulates the expression of KLF2 gene in several HCC cell lines. KLF2 protein is able to inhibit TGF-β/Smad signaling in HCC cells as assessed by luciferase reporter assay. Further studies indicated that KLF2 inhibits the transcriptional activity of Smad2/3 and Smad4 and ameliorates TGF-β-induced target gene expression, therefore creating a novel negative feedback loop in TGF-β signaling. Functionally, stably expression of KLF2 in HCCLM3 cells attenuated TGF-β-induced cancer cell motility in wound-healing and transwell assays by interfering with TGF-β-mediated upregulation of MMP2. Together, our results revealed that KLF2 protein has a tumor-suppressive function in HCC through a negative feedback loop over TGF-β signaling.

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