LRP16 Promotes Proliferation and Migration of Esophageal Squamous Cell Carcinoma by Regulating Hippo Signaling Pathway

2021 ◽  
Author(s):  
Cong Liu ◽  
Chao Xiong ◽  
Xianzeng Wang ◽  
Ting Sun ◽  
Zhenzhen Ren ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Cell Counting ◽  
Depth Of Invasion ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Normal Tissues ◽  
M Phase ◽  
Formation Experiment ◽  
And Migration

Abstract The present study aimed to investigate the expression of LRP16 in the development of ESCC and the relationship between Hippo signaling pathway and LRP16. Immunohistochemistry was used to detect the expression of LRP16 in ESCC tissues. After transfection, the expression of LRP16 was detected by reverse transcription quantitative PCR (RT-qPCR) and western blot techniques. Cell counting kit (CCK-8), clone formation experiment, flow cytometry and wound healing were used to determine the proliferation, apoptosis, cell cycle and migration of ESCC cells. The changes of factors related to Hippo signaling pathway were determined via RT-qPCR and western blot experiments. The results showed that the LRP16 expression in ESCC tissues was higher than that in normal tissues. High expression of LRP16 was related to the depth of invasion, TNM stage and lymph node metastasis of ESCC. Furthermore, the knockdown of LRP16 inhibited proliferation, migration and promoted cell apoptosis and made cells arrested in G2/M phase. It also resulted in decreased expression of Yes-associated protein (YAP), and increased expression of mammalian STE20-like protein kinase (MST1/2), suggesting that LRP16 promoted the development of ESCC through Hippo signaling pathway. The results of this study suggest that LRP16 may be a carcinogenic gene of ESCC and promotes the progression of ESCC through the regulation of Hippo signaling pathway. Our study provides a new idea for the diagnosis and treatment of ESCC in the future.

scholarly journals Nitidine chloride possesses anticancer property in lung cancer cells through activating Hippo signaling pathway

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Jing Zhang ◽  
Linhui Wu ◽  
Chaoqun Lian ◽  
Shuo Lian ◽  
Shimeng Bao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Western Blot ◽  
Signaling Pathway ◽  
Migration And Invasion ◽  
Hippo Signaling ◽  
Protein Expression Level ◽  
Hippo Signaling Pathway ◽  
Proliferation Ability ◽  
And Migration ◽  
Western Blot Data

Abstract Nitidine chloride (NC) has significant anti-tumor properties; however, the precise mechanism related to NC still needs further investigation. This study intends to investigate the anti-tumor functions and the feasible molecular basis of NC in NSCLC cells. Therefore, we determined the mechanism of NC-mediated anti-tumor function through various methods. Cell proliferation ability and migration and invasion were detected by CCK-8, colony formation assay and Transwell assay, respectively. Furthermore, flow cytometry was used to detect apoptosis, cell cycle and ROS. Moreover, protein expression level was measured by western blot. Our results showed that NC can inhibit the growth, motility of NSCLC cells, induce apoptosis and arrest cell cycle. Meanwhile, NC increased the level of ROS in NSCLC cells. Moreover, western blot data showed that NC suppressed the expression of Lats1, Mob1, and YAP, and enhanced the expression of p-Lats1, p-Mob1, p-YAP1 (ser127). Overall, our research reveals that NC exerts anticancer activity by activating and modulating the Hippo signaling pathway.

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.

scholarly journals Hsa_circ_0005273 regulates YAP1-Hippo signaling pathway by targeting miR-200a-3p to promote breast cancer progression.

2020 ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Qifeng Luo ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Potential Biomarker ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background : Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functions of hsa_circ_0005273 in breast cancer remains unknown. Here we aim to explore the role of hsa_circ_0005273 in BC. Methods : We chose miR-200a-3p as the potential target of hsa_circ_0005273. The expression levels of hsa_circ_0005273 and miR-200a-3p were examined in BC tissues compared with adjacent normal tissues by qRT-PCR. To characterize the function of hsa_circ_0005273, experiments of cell proliferation and migration were performed in BC cell lines infected with lentivirus targeting hsa_circ_0005273. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. Luciferase reporter assay was conducted to confirm the relationship between hsa_circ_0005273 and miR-200a-3p as well as miR-200a-3p andYAP1. Results : Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of has_circ_0005273 or upregulation of miR-200a-3p inhibited the proliferation and migration of BC cells in vitro and vivo. Mechanistically, hsa_circ_0005273 upregulated YAP1 by targeting miR-200a-3p and activated Hippo signaling pathway to promote BC progression. Conclusions : Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and activates Hippo signaling pathway to promote BC progression, and it may serve as a potential biomarker and therapeutic target. Keywords : breast cancer, hsa_circ_0005273, miR-200a-3p,YAP1, progression

scholarly journals Role of YAP1 gene in proliferation and osteogenic differentiation of human periodontal ligament stem cells induced by TNF-α

2020 ◽  
Author(s):  
Tao Dong ◽  
Xuemin Sun ◽  
He Jin
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Signaling Pathway ◽  
Hippo Signaling ◽  
Related Protein ◽  
Periodontal Ligament Stem Cells ◽  
Hippo Signaling Pathway ◽  
Tnf Α ◽  
Related Proteins

AbstractBackgroundPeriodontitis is a chronic inflammatory disease that occurs in periodontal tissues and can cause tooth loosening and loss in severe cases. As the main effector of downstream of Hippo signaling pathway, Yes-related protein 1 (YAP1) plays an important role in cell proliferation and differentiation. However, the role of YAP1 in periodontitis has not been reported.MethodsCell activity was detected by CCk-8. YAP1 was overexpressed by cell transfection, and then RT-qPCR and western blot were used to detect the expression of YAP1. The cell proliferation was determined by clone formation assay, and the expression of proliferation-related proteins was determined by western blot. The cell differentiation was detected by Elisa kit of ALP and alizarin red staining. Finally, western blot was used to detect the expression of differentiation-related protein and Hippo signaling pathway-related proteins.ResultsWith the increase of concentration induced by TNF-α, the cell survival rate of human periodontal ligament stem cells (HPDLSC) decreased significantly. After the overexpression of YAP1, cell proliferation and proliferation-related protein expression increased. Overexpression of YAP1 can improve the differentiation and the formation of osteoblasts of HPDLSCs induced by TNF-α. The expression of Hippo signaling pathway-related proteins transcriptional coactivators with PDZ binding domains (TAZ), TEA domain family member (TRED) increased and proliferation-related protein P27 decreased.ConclusionTNF-α can inhibit proliferation and osteogenic differentiation of HPDLSCs, which can be ameliorated by the YAP1 gene through the Hippo signaling pathway. Our paper suggested that YAP1 may be a potential therapeutic target for periodontitis.

scholarly journals Mechanical Strain Regulates Myofibroblast Differentiation of Human Scleral Fibroblasts by YAP

2021 ◽  
Vol 12 ◽  
Author(s):  
Di Hu ◽  
Junhong Jiang ◽  
Baiyang Ding ◽  
Kang Xue ◽  
Xinghuai Sun ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Western Blotting ◽  
Mechanical Strain ◽  
Cell Counting ◽  
Type I ◽  
Myofibroblast Differentiation ◽  
Hippo Signaling ◽  
Ecm Remodeling ◽  
Expression Levels ◽  
Hippo Signaling Pathway

Scleral extracellular matrix (ECM) remodeling is thought to play a critical role in the pathogenesis of glaucoma. Mechanical strain induced by elevated intraocular pressure can promote myofibroblast differentiation of fibroblasts and result in scleral ECM remodeling; however, the underlying mechanism remains poorly understood. Yes-associated protein (YAP) is a mechanosensory protein and the key downstream transcriptional effector of the Hippo signaling pathway. Here, we investigated the role of YAP in mechanical strain-induced myofibroblast transformation during glaucoma scleral ECM remodeling. Integrative bioinformatics analyses were performed to identify the key pathways for the ECM remodeling of the sclera in glaucoma. Sprague–Dawley rats were used to establish a chronic ocular hypertension model, and the expression of collagen type I (COL1) and YAP in the sclera was analyzed by immunohistochemical analysis and Western blotting. Furthermore, human scleral fibroblasts (HSFs) were cultured and subjected to mechanical strain. In groups with or without the YAP siRNA or YAP inhibitor, cell proliferation, migration capacity, and the expression levels of YAP, COL1, and α-smooth muscle actin (α-SMA) were evaluated by Cell Counting Kit-8 assay, scratch assay, and Western blotting. The interactions between YAP and Smad3 were demonstrated by coimmunoprecipitation, and the expression levels of COL1 and α-SMA were evaluated in groups treated with or without the Smad3 inhibitor. We first revealed that the Hippo signaling pathway may be involved in mechanical strain-induced scleral ECM remodeling through bioinformatics analysis. Furthermore, the in vivo study showed upregulated YAP, COL1, and α-SMA expression in the hypertensive sclera of rats. In vitro, mechanical strain increased YAP and COL1 expression in HSFs and promoted myofibroblast differentiation. After YAP knockdown or inhibition with verteporfin, mechanical strain-induced fibrotic changes in HSFs were markedly suppressed. Additionally, YAP showed a protein interaction with Smad3, and the upregulation of a-SMA and COL1 in response to mechanical strain was also significantly downregulated following the inhibition of Smad3. In conclusion, mechanical strain activated scleral myofibroblast differentiation via YAP. The YAP pathway may play an important role in regulating scleral myofibroblast differentiation and ECM remodeling of the sclera in glaucoma.

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.

scholarly journals Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model

2021 ◽  
Vol 22 (2) ◽  
pp. 931
Author(s):  
Jihyun Lee ◽  
Yujin Jung ◽  
Seo won Jeong ◽  
Ga Hee Jeong ◽  
Gue Tae Moon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Normal Skin ◽  
Skin Lesions ◽  
Hippo Signaling ◽  
Vascular Endothelial ◽  
Expression Levels ◽  
Hippo Signaling Pathway ◽  
Endothelial Growth Factor

The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea.

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