scholarly journals Overexpressed WDR3 Induces the Activation of Hippo Pathway by Interacting with GATA4 in Pancreatic Cancer

2020 ◽  
Author(s):  
Wenjie Su ◽  
Shikai Zhu ◽  
Kai Chen ◽  
Hongji Yang ◽  
Mingwu Tian ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Human Cancer ◽  
Critical Role ◽  
Biological Role ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Pancreatic Cancer Cells ◽  
Independent Functions

Abstract Background: WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer.Methods: The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions.Results: Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, in pancreatic cancer cells.Conclusions: We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through an interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.

scholarly journals Overexpressed WDR3 induces the activation of Hippo pathway by interacting with GATA4 in pancreatic cancer

2021 ◽  
Author(s):  
Wenjie Su ◽  
Shikai Zhu ◽  
Kai Chen ◽  
Hongji Yang ◽  
Mingwu Tian ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Critical Role ◽  
Biological Role ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Pancreatic Cancer Cells ◽  
Independent Functions

Abstract Background: WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer.Methods: The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions.Results: Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion, and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, which interaction induced the nuclear translocation of GATA4 in pancreatic cancer cells.Conclusions: We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through the interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.

scholarly journals Overexpressed WDR3 induces the activation of Hippo pathway by interacting with GATA4 in pancreatic cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Wenjie Su ◽  
Shikai Zhu ◽  
Kai Chen ◽  
Hongji Yang ◽  
Mingwu Tian ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Critical Role ◽  
Biological Role ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Pancreatic Cancer Cells ◽  
Independent Functions

Abstract Background WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer. Methods The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions. Results Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion, and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, which interaction induced the nuclear translocation of GATA4 in pancreatic cancer cells. Conclusions We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through the interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.

scholarly journals Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Potential Biomarker

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

The emerging role of Hippo signaling pathway in regulating osteoclast formation

2018 ◽  
Vol 233 (6) ◽  
pp. 4606-4617 ◽  
Author(s):  
Wanlei Yang ◽  
Weiqi Han ◽  
An Qin ◽  
Ziyi Wang ◽  
Jiake Xu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Osteoclast Formation ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

scholarly journals The Hippo Signaling Pathway in Pancreatic Cancer

2019 ◽  
Vol 39 (7) ◽  
pp. 3317-3321 ◽  
Author(s):  
DANIEL ANSARI ◽  
HENRIK OHLSSON ◽  
CARL ALTHINI ◽  
MONIKA BAUDEN ◽  
QIMIN ZHOU ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

Abstract MP239: Hippo Signaling Pathway Maintains Homeostasis Of The Cardiac Conduction System

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Mingjie Zheng ◽  
Jun Wang
Keyword(s):  
Signaling Pathway ◽  
Calcium Homeostasis ◽  
Cardiac Arrhythmias ◽  
Critical Role ◽  
Conduction System ◽  
Conditional Knockout ◽  
Cardiac Conduction ◽  
Cardiac Conduction System ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

The cardiac conduction system (CCS) is required for initiating and maintaining regular rhythmic heartbeats. The fundamental Hippo signaling pathway plays critical roles in the heart, yet its role in the CCS remains largely unknown. Here, we found that conditional knockout (CKO) of Hippo signaling kinases Lats1 and Lats2 in the CCS using Hcn4 CreERT2 , led to cardiac arrhythmias in adult mice. Compared with controls, Lats1/2 CKO mutant mice had disrupted calcium homeostasis, increased fibrosis and more fibroblast proliferation in the sinoatrial node. Deletion of the Hippo signaling effectors Yap and Taz in the CCS rescued phenotypes caused by Lats1/2 deletion, and these mice had rescued sinus rhythm and reduced fibrosis, which indicated that Lats1/2 function through Yap and Taz in CCS. Our Cleavage Under Targets and Tagmentation (CUT&Tag)-sequencing using Yap antibody followed by RNA-Seq revealed that Yap directly regulates calcium homeostasis genes such as Ryr2 and fibrosis induction genes such as TGF-β family. Further, we discovered that miR-17-92 represses Hippo signaling by directly suppressing Lats2 expression. miR-17-92 CKO in the CCS led to increased Hippo signaling activity and cardiac arrhythmias, indicating that a fine-tuned level of Hippo signaling is critical for CCS homeostasis. Together, our findings reveal the critical role of a miR-Hippo-Yap genetic pathway in maintaining CCS homeostasis.

Abemaciclib induces apoptosis in cardiomyocytes by activating the Hippo signaling pathway

2020 ◽  
Vol 52 (8) ◽  
pp. 875-882
Author(s):  
Yajie Zhou ◽  
Yanfei Li ◽  
Junwei Shen ◽  
Jue Li ◽  
Xinming Li
Keyword(s):  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Cell Counting ◽  
Hippo Signaling ◽  
Cyclin Dependent Kinase ◽  
Cardiac Side Effects ◽  
Hippo Signaling Pathway ◽  
The Us ◽  
Induced Apoptosis

Abstract Abemaciclib is the newest cyclin-dependent kinase 4/6 inhibitor that has received approval from the US Food and Drug Administration for using in patients with advanced breast cancer. However, its potential adverse effects on cardiomyocytes remain unknown. In this study, we used the cell counting kit-8 assay, western blot analysis, flow cytometry, immunostaining, and quantitative polymerase chain reaction to investigate the role of abemaciclib in inducing apoptosis and in inhibiting the viability and proliferation of AC16 human cardiomyocyte cells. The results revealed that abemaciclib induced apoptosis and inhibited cell proliferation by activating the Hippo signaling pathway. This work demonstrates the molecular basis by which abemaciclib induces cardiac side effects, providing a theoretical basis and effective targets for the treatment of cardiac diseases.

Sign in / Sign up

Export Citation Format

Share Document