scholarly journals High expression of SMYD3 indicates poor survival outcome and promotes tumour progression through an IGF-1R/AKT/E2F-1 positive feedback loop in bladder cancer

Aging ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 2030-2048 ◽  
Author(s):  
Guoliang Wang ◽  
Yi Huang ◽  
Feilong Yang ◽  
Xiaojun Tian ◽  
Kun Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Tumour Progression ◽  
Survival Outcome ◽  
High Expression ◽  
Poor Survival ◽  
Positive Feedback Loop ◽  
Poor Survival Outcome

scholarly journals An HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis

2021 ◽  
Author(s):  
Changhao Chen ◽  
Yuting Li ◽  
Yuming Luo ◽  
Hanhao Zheng ◽  
Yan Lin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Positive Feedback ◽  
Noncoding Rna ◽  
Feedback Loop ◽  
Xenograft Model ◽  
Positive Feedback Loop ◽  
Reciprocal Interactions ◽  
Orthotopic Xenograft Model ◽  
Bladder Cancer Cells

Abstract Cancer-associated fibroblasts (CAFs) are essential etiologic actors in promoting tumor progression via extensive reciprocal interactions with cancer cells. Yet, the biological role and regulatory mechanism of CAFs phenotype underlying lymph node (LN) metastasis of bladder cancer (BCa) remain unclear. Here, we report that BCa cell-secreted extracellular vesicles (EVs) played an important role in the CAF-enriched microenvironment, which correlated with BCa lymphangiogenesis and LN metastasis. RNA sequencing identified an EV-associated long noncoding RNA, LINC00665, which acted as a crucial mediator of CAF infiltration in BCa. LINC00665 mediated EV release from BCa cells to endow fibroblasts with the CAF phenotype, which reciprocally induced LINC00665 upregulation to form a RAB27B-HGF-c-Myc positive feedback loop, facilitating BCa lymphangiogenesis and LN metastasis. Importantly, we demonstrate that Cabozantinib significantly suppressed LINC00665-mediated BCa LN metastasis in an orthotopic xenograft model. Our study highlights a molecular mechanism by which LINC00665 induces a RAB27B-HGF-c-Myc positive feedback loop between cancer cells and fibroblasts to sustain BCa LN metastasis, and represents LINC00665 as a potential therapeutic target in BCa LN metastasis.

scholarly journals High expression of GPR116 indicates poor survival outcome and promotes tumor progression in colorectal carcinoma

Oncotarget ◽  
2017 ◽  
Vol 8 (29) ◽  
pp. 47943-47956 ◽  
Author(s):  
Li Yang ◽  
Xiao-Lu Lin ◽  
Wei Liang ◽  
Seng-Wang Fu ◽  
Wen-Feng Lin ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Tumor Progression ◽  
Survival Outcome ◽  
High Expression ◽  
Poor Survival ◽  
Poor Survival Outcome

scholarly journals A Positive Feedback Loop Ensures Propagation of ROS Production and JNK Signaling Throughout Drosophila Tissue Regeneration

2017 ◽  
Author(s):  
Sumbul Jawed Khan ◽  
Syeda Nayab Fatima Abidi ◽  
Andrea Skinner ◽  
Yuan Tian ◽  
Rachel K. Smith-Bolton
Keyword(s):  
Reactive Oxygen Species ◽  
Differentially Expressed Genes ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Transcriptional Profiling ◽  
High Expression ◽  
Oxygen Species ◽  
Positive Feedback Loop ◽  
Jnk Signaling ◽  
Regenerative Growth

AbstractRegenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed wholegenome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescent labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by wholegenome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth.Author summaryRegenerating tissue must initiate the signaling that drives regenerative growth, and then sustain that signaling long enough for regeneration to complete. Drosophila imaginal discs, the epithelial structures in the larva that will form the adult animal during metamorphosis, have been an important model system for tissue repair and regeneration for over 60 years. Here we show that damage-induced JNK signaling leads to the upregulation of a gene called moladietz, which encodes a co-factor for an enzyme, NADPH dual oxidase (DUOX), that generates reactive oxygen species (ROS), a key tissue-damage signal. High expression of moladietz induces continuous production of ROS in the regenerating tissue. The sustained production of ROS then continues to activate JNK signaling throughout the course of regeneration, ensuring maximal tissue regrowth.

scholarly journals A Feedback Loop Formed by ATG7/Autophagy, FOXO3a/miR-145 and PD-L1 Regulates Stem-Like Properties and Invasion in Human Bladder Cancer

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 349 ◽  
Author(s):  
Junlan Zhu ◽  
Yang Li ◽  
Yisi Luo ◽  
Jiheng Xu ◽  
Huating Liufu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Positive Feedback ◽  
Mrna Stability ◽  
Feedback Loop ◽  
Immune Checkpoint Blockade ◽  
Immune Checkpoints ◽  
Positive Feedback Loop ◽  
Direct Binding ◽  
L1 Protein ◽  
Cell Death Protein

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 blockade have been identified to target immune checkpoints to treat human cancers with durable clinical benefit. Several studies reveal that the response to PD-1-PD-L1 blockade might correlate with PD-L1 expression levels in tumor cells. However, the mechanistic pathways that regulate PD-L1 protein expression are not understood. Here, we reported that PD-L1 protein is regulated by ATG7-autophagy with an ATG7-initiated positive feedback loop in bladder cancer (BC). Mechanistic studies revealed that ATG7 overexpression elevates PD-L1 protein level mainly through promoting autophagy-mediated degradation of FOXO3a, thereby inhibiting its initiated miR-145 transcription. The lower expression of miR-145 increases pd-l1 mRNA stability due to the reduction of its direct binding to 3′-UTR of pd-l1 mRNA, in turn leading to increasing in pd-l1 mRNA stability and expression, and finally enhancing stem-like property and invasion of BC cells. Notably, overexpression of PD-L1 in ATG7 knockdown cells can reverse the defect of autophagy activation, FOXO3A degradation, and miR-145 transcription attenuation. Collectively, our results revealed a positive feedback loop to promoting PD-L1 expression in human BC cells. Our study uncovers a novel molecular mechanism for regulating pd-l1 mRNA stability and expression via ATG7/autophagy/FOXO3A/miR-145 axis and reveals the potential for using combination treatment with autophagy inhibitors and PD-1/PD-L1 immune checkpoint blockade to enhance therapeutic efficacy for human BCs.

scholarly journals A positive feedback loop between TAZ and miR-942-3p modulates proliferation, angiogenesis, epithelial-mesenchymal transition process, glycometabolism and ROS homeostasis in human bladder cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Feifan Wang ◽  
Mengjing Fan ◽  
Xuejian Zhou ◽  
Yanlan Yu ◽  
Yueshu Cai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Epithelial Mesenchymal Transition ◽  
Biological Functions ◽  
Positive Feedback Loop ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
Bladder Cancer Cells

Abstract Background Transcriptional coactivator with PDZ-binding motif (TAZ) has been reported to be involved in tumor progression, angiogenesis, epithelial-mesenchymal transition (EMT), glycometabolic modulation and reactive oxygen species (ROS) buildup. Herein, the underlying molecular mechanisms of the TAZ-induced biological effects in bladder cancer were discovered. Methods qRT-PCR, western blotting and immunohistochemistry were performed to determine the levels of TAZ in bladder cancer cells and tissues. CCK-8, colony formation, tube formation, wound healing and Transwell assays and flow cytometry were used to evaluate the biological functions of TAZ, miR-942-3p and growth arrest-specific 1 (GAS1). QRT-PCR and western blotting were used to determine the expression levels of related genes. Chromatin immunoprecipitation and a dual-luciferase reporter assay were performed to confirm the interaction between TAZ and miR-942. In vivo tumorigenesis and colorimetric glycolytic assays were also conducted. Results We confirmed the upregulation and vital roles of TAZ in bladder cancer. TAZ-induced upregulation of miR-942-3p expression amplified upstream signaling by inhibiting the expression of large tumor suppressor 2 (LATS2, a TAZ inhibitor). MiR-942-3p attenuated the impacts on cell proliferation, angiogenesis, EMT, glycolysis and ROS levels induced by TAZ knockdown. Furthermore, miR-942-3p restrained the expression of GAS1 to modulate biological behaviors. Conclusion Our study identified a novel positive feedback loop between TAZ and miR-942-3p that regulates biological functions in bladder cancer cells via GAS1 expression and illustrated that TAZ, miR-942-3p and GAS1 might be potential therapeutic targets for bladder cancer treatment.

scholarly journals LncRNA PVT1 Promotes Bladder Cancer Progression by Forming a Positive Feedback Loop With STAT5B

2021 ◽  
Author(s):  
Zhuo Li ◽  
Jian Liu ◽  
Huifeng Fu ◽  
Yuanwei Li ◽  
Qaing Lu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter ◽  
Positive Feedback Loop ◽  
Rna Immunoprecipitation ◽  
Transcriptional Effect

Abstract Background: Plasmacytoma Variant Translocation 1 (LncRNA PVT1) and signal transducer and activator of transcription 5B (STAT5B) have been reported to play important roles in various cancers, but their interaction in bladder cancer (BC) remains unclear. Purpose: In this study, we aimed to explore the interaction between lncRNA PVT1 and STAT5B in BC tumorigenesis. Methods: The association of the expression of the lncRNA PVT1 and STAT5B to the prognosis of patient with BC was evaluated via bioinformatic analysis. Loss- and gain-of-function assays were performed to determine the biological functions of lncRNA PVT1 and STAT5B in BC cells. Quantitative real time polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence were used to detect lncRNA PVT1 and STAT5B expression. Fluorescence in situ hybridization, RNA pull-down and RNA immunoprecipitation assays were conducted to determine the regulatory effect of lncRNA PVT1 on STAT5B. The transcriptional effect of STAT5B on lncRNA PVT1 gene was determined using luciferase reporter assay, chromatin immunoprecipitation and DNA-affinity precipitation assays.Results: We found that lncRNA PVT1 and STAT5B enhance the expression of each other and promote the malignant phenotypes in BC, including cell viability and invasion. lncRNA PVT1 stabilizes STAT5B by decreasing ubiquitination, enhances STAT5B phosphorylation, and promotes the translocation to the nucleus of STAT5B to trigger further carcinogenesis activities. In the nucleus, STAT5B activates the transcription of lncRNA PVT1 by binding directly to its promoter region, leading to a positive feedback.Conclusions: We first identified the lncRNA PVT1/STAT5B positive feedback loop for bladder carcinogenesis, which may provide new molecular targets for interventions of BC.

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