scholarly journals DEAD-box protein p68 is regulated by β-catenin/transcription factor 4 to maintain a positive feedback loop in control of breast cancer progression

2014 ◽  
Vol 16 (6) ◽  
Author(s):  
Kiran Kumar Naidu Guturi ◽  
Moumita Sarkar ◽  
Arijit Bhowmik ◽  
Nilanjana Das ◽  
Mrinal Kanti Ghosh
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Progression ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Breast Cancer Progression ◽  
Positive Feedback Loop ◽  
Dead Box ◽  
Transcription Factor 4

scholarly journals AKR1B1 promotes basal-like breast cancer progression by a positive feedback loop that activates the EMT program

2017 ◽  
Vol 214 (4) ◽  
pp. 1065-1079 ◽  
Author(s):  
Xuebiao Wu ◽  
Xiaoli Li ◽  
Qiang Fu ◽  
Qianhua Cao ◽  
Xingyu Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Positive Feedback ◽  
Poor Prognosis ◽  
Feedback Loop ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Patients ◽  
Positive Feedback Loop ◽  
Mesenchymal Transition ◽  
Basal Like Breast Cancer

Basal-like breast cancer (BLBC) is associated with high-grade, distant metastasis and poor prognosis. Elucidating the determinants of aggressiveness in BLBC may facilitate the development of novel interventions for this challenging disease. In this study, we show that aldo-keto reductase 1 member B1 (AKR1B1) overexpression highly correlates with BLBC and predicts poor prognosis in breast cancer patients. Mechanistically, Twist2 transcriptionally induces AKR1B1 expression, leading to nuclear factor κB (NF-κB) activation. In turn, NF-κB up-regulates Twist2 expression, thereby fulfilling a positive feedback loop that activates the epithelial–mesenchymal transition program and enhances cancer stem cell (CSC)–like properties in BLBC. AKR1B1 expression promotes, whereas AKR1B1 knockdown inhibits, tumorigenicity and metastasis. Importantly, epalrestat, an AKR1B1 inhibitor that has been approved for the treatment of diabetic complications, significantly suppresses CSC properties, tumorigenicity, and metastasis of BLBC cells. Together, our study identifies AKR1B1 as a key modulator of tumor aggressiveness and suggests that pharmacologic inhibition of AKR1B1 has the potential to become a valuable therapeutic strategy for BLBC.

Involvement of NAC transcription factor SiNAC1 in a positive feedback loop via ABA biosynthesis and leaf senescence in foxtail millet

Planta ◽  
2017 ◽  
Vol 247 (1) ◽  
pp. 53-68 ◽  
Author(s):  
Tingting Ren ◽  
Jiawei Wang ◽  
Mingming Zhao ◽  
Xiaoming Gong ◽  
Shuxia Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Leaf Senescence ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Foxtail Millet ◽  
Nac Transcription Factor ◽  
Positive Feedback Loop ◽  
Aba Biosynthesis

scholarly journals A Positive Feedback Loop of lncRNA MIR31HG-miR-361-3p -YY1 Accelerates Colorectal Cancer Progression Through Modulating Proliferation, Angiogenesis, and Glycolysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Guo ◽  
Defeng Liu ◽  
Shihao Peng ◽  
Meng Wang ◽  
Yangyang Li
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Positive Feedback Loop ◽  
Related Proteins

BackgroundColorectal cancer (CRC) is a common malignant tumor with high metastatic and recurrent rates. This study probes the effect and mechanism of long non-coding RNA MIR31HG on the progression of CRC cells.Materials and MethodsQuantitative real-time PCR (qRT-PCR) was used to analyze the expression of MIR31HG and miR-361-3p in CRC tissues and normal tissues. Gain- or loss-of-function assays were conducted to examine the roles of MIR31HG, miR-361-3p and YY1 transcription factor (YY1) in the CRC progression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and colony formation experiment were conducted to test CRC cell proliferation. CRC cell invasion was determined by Transwell assay. The glucose detection kit and lactic acid detection kit were utilized to monitor the levels of glucose and lactate in CRC cells. The glycolysis level in CRC cells was examined by the glycolytic stress experiment. Western blot was performed to compare the expression of glycolysis-related proteins (PKM2, GLUT1 and HK2) and angiogenesis-related proteins (including VEGFA, ANGPT1, HIF1A and TIMP1) in HUVECs. The binding relationships between MIR31HG and miR-361-3p, miR-361-3p and YY1 were evaluated by the dual-luciferase reporter assay and RNA immunoprecipitation (RIP).ResultsMIR31HG was up-regulated in CRC tissues and was associated with poorer prognosis of CRC patients. The in-vitro and in-vivo experiments confirmed that overexpressing MIR31HG heightened the proliferation, growth, invasion, glycolysis and lung metastasis of CRC cells as well as the angiogenesis of HUVECs. In addition, MIR3HG overexpression promoted YY1 mRNA and protein level, and forced overexpression of YY1 enhanced MIR31HG level. Overexpressing YY1 reversed the tumor-suppressive effect mediated by MIR31HG knockdown. miR-361-3p, which was inhibited by MIR31HG overexpression, repressed the malignant behaviors of CRC cells. miR-361-3p-mediated anti-tumor effects were mostly reversed by upregulating MIR31HG. Further mechanism studies illustrated that miR-361-3p targeted and negatively regulated the expression of YY1.ConclusionThis study reveals that MIR31HG functions as an oncogenic gene in CRC via forming a positive feedback loop of MIR31HG-miR-361-3p-YY1.

scholarly journals The Establishment of CDK9/ RNA PolII/H3K4me3/DNA Methylation Feedback Promotes HOTAIR Expression by RNA Elongation Enhancement in Cancer

2019 ◽  
Author(s):  
Chi Hin Wong ◽  
Chi Han Li ◽  
Qifang He ◽  
Joanna Hung Man Tong ◽  
Ka-Fai To ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cancer Progression ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Transcription Elongation ◽  
Underlying Mechanism ◽  
Transcriptional Elongation ◽  
Gene Body ◽  
Gene Body Methylation ◽  
Positive Feedback Loop

SUMMARYLong non-coding RNA HOX Transcript Antisense RNA (HOTAIR) is overexpressed in multiple cancers with diverse genetic profiles, which heavily contributed to cancer progression. However, the underlying mechanism leading to HOTAIR deregulation is largely unexplored. Here, we revealed that gene body methylation promoted HOTAIR expression through enhancing the transcription elongation process in cancer. We linked up the aberrant gene body histone and DNA methylation in promoting transcription elongation via phosphorylation of Polymerase II Ser 2 by CDK7-CDK9, and elucidated the mechanism of a positive feedback loop involving CDK7, MLL1 and DNMT3A in promoting gene body methylation and overexpressing HOTAIR. To our knowledge, this is the first time to demonstrate that a positive feedback loop that involved CDK9-mediated phosphorylation of PolII and histone and gene body methylation induced robust transcriptional elongation, which heavily contributed to the upregulation of oncogenic lncRNA in cancer.

scholarly journals A Positive Feedback Loop Between Gastric Cancer Cells and Tumor-associated Macrophage Induces Malignancy Progression

2022 ◽  
Author(s):  
Haiyan Piao ◽  
Lingfeng Fu ◽  
Yang Liu ◽  
Yue Wang ◽  
Xiangyu Meng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Nuclear Factor Kappa B ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
Positive Feedback Loop ◽  
Nuclear Factor Kappa

Abstract Background: Hypoxia and inflammation tumor microenvironment (TME) play a crucial role in tumor development and progression. Although increased understanding of TME contributed to gastric cancer (GC) progression and prognosis, the direct interaction between macrophage and GC cells was not fully understood.Methods: Hypoxia and normoxia macrophage microarrays of GEO database was analyzed. The peripheral blood mononuclear cell acquired from the healthy volunteers. The expression of CXCL8 in GC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR), western-blot, Elisa and immunofluorescence. Cell proliferation, migration, and invasion were evaluated by cell counting kit 8 (CCK8), colony formation, real-time imaging of cell migration and transwell. Luciferase reporter assays and chromatin immunoprecipitation were used to identify the interaction between transcription factor and target gene. Especially, a series of truncated and mutation reporter genes were applied to identify precise binding sites.The corresponding functions were verified in the complementation test and in vivo animal experiment.Results: Our results revealed that Hypoxia triggered macrophage secreted C-X-C Motif Chemokine Ligand 8 (CXCL8), which induced GC invasion and proliferation. This macrophage-induced GC progression was CXCL8 activated C-X-C Motif Chemokine Receptor 1/2 (CXCR1/2) on the GC cell membrane subsequently hyperactivated Janus kinase 1/ Signal transducer and activator of transcription 1 (JAK/STAT1) signaling pathway. Then, the transcription factor STAT1 directly led to the overexpression and secretion of Interleukin 10 (IL-10). Correspondingly, IL-10 induced the M2-type polarization of macrophages through the Nuclear Factor kappa B (NF-κB) pathway-dependent mechanism and continued to increase the expression and secretion of CXCL8 through the transcription factor Nuclear Factor Kappa B Subunit 1 (NFKB1, p50). It suggested a positive feedback loop between macrophage and GC. In clinical GC samples, increased CXCL8 predicted a patient's pessimistic outcome.Conclusion: Our work identified a positive feedback loop governing cancer cells and macrophage in GC that contributed to tumor progression and patient outcome.

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