scholarly journals Sequence Analysis and Homology Modeling of NF2 Protein

2019 ◽  
pp. 373-377
Author(s):  
Vinod P. Sinoorkar ◽  
Pratiksha S. Thakurdas
Keyword(s):  
Cell Death ◽  
Signaling Pathway ◽  
Actin Binding ◽  
Hippo Signaling ◽  
Β Cell ◽  
Neurofibromatosis 2 ◽  
Pancreatic Cell ◽  
Hippo Signaling Pathway ◽  
Molecular Features ◽  
Chronic Hyperglycemia

Diabetes is diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. In India more than 62 million individuals currently diagnosed with the diabetes. Diabetes is resulting from insulin deficiency or pancreatic cells become insulin resistant. Pancreatic cell (β-cell) death by apoptosis is one of main reason which results in diabetic condition in patients. Neurofibromatosis 2 is involved is β-cell death. Neurofibromatosis 2 (NF2/Merlin) is a tumor suppressor protein, which belongs to the ezrin–radixin–moesin family of actin-binding proteins and regulates the Hippo signaling pathway in mammals and also involved in the regulation of cell proliferation and apoptosis. Merlin regulates the Hippo signaling pathway by controlling the Hippo kinases cassettes MST1/2 and LATS1/2. Therefore, targeting β-cell apoptosis and dysfunction can be a therapeutic approach for the treatment of diabetes. Hence our present investigation focus mainly to understand the detailed molecular features of NF2 by its protein sequence annotation by implementing tools and techniques of Bioinformatics.

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.

scholarly journals NF2 and Canonical Hippo-YAP Pathway Define Distinct Tumor Subsets Characterized by Different Immune Deficiency and Treatment Implications in Human Pleural Mesothelioma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1561
Author(s):  
Haitang Yang ◽  
Sean R. R. Hall ◽  
Beibei Sun ◽  
Liang Zhao ◽  
Yanyun Gao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Checkpoint Inhibitors ◽  
Cancer Cell Line ◽  
Cell Mediated Immunity ◽  
Pleural Mesothelioma ◽  
Precision Oncology ◽  
Hippo Signaling ◽  
Loss Of Function ◽  
Cell Viability Assay ◽  
Molecular Features

(1) Inactivation of the tumor suppressor NF2 is believed to play a major role in the pathogenesis of malignant pleural mesothelioma (MPM) by deregulating the Hippo-YAP signaling pathway. However, NF2 has functions beyond regulation of the Hippo pathway, raising the possibility that NF2 contributes to MPM via Hippo-independent mechanisms. (2) We performed weighted gene co-expression analysis (WGCNA) in transcriptomic and proteomic datasets obtained from The Cancer Gene Atlas (TCGA) MPM cohort to identify clusters of co-expressed genes highly correlated with NF2 and phospho (p)-YAP protein, surrogate markers of active Hippo signaling and YAP inactivation. The potential targets are experimentally validated using a cell viability assay. (3) MPM tumors with NF2 loss-of-function are not associated with changes in p-YAP level nor YAP/TAZ activity score, but are characterized by a deficient B-cell receptor (BCR) signaling pathway. Conversely, MPM tumors with YAP activation display exhausted CD8 T-cell-mediated immunity together with significantly upregulated PD-L1, which is validated in an independent MPM cohort, suggesting a potential benefit of immune-checkpoint inhibitors (ICI) in this patient subset. In support of this, mutations in core Hippo signaling components including LATS2, but not NF2, are independently associated with better overall survival in response to ICI in patients. Additionally, based on cancer cell line models, we show that MPM cells with a high Hippo-YAP activity are particularly sensitive to inhibitors of BCR-ABL/SRC, stratifying a unique MPM patient subset that may benefit from BCR-ABL/SRC therapies. Furthermore, we observe that NF2 physically interacts with a considerable number of proteins that are not involved in the canonical Hippo-YAP pathway, providing a possible explanation for its Hippo-independent role in MPM. Finally, survival analyses show that YAP/TAZ scores together with p-YAP protein level, but not NF2, predict the prognosis of MPM patients. (4) NF2 loss-of-function and dysregulated Hippo-YAP pathway define distinct MPM subsets that differ in their molecular features and prognosis, which has important clinical implications for precision oncology in MPM patients.

Roles of Hippo signaling pathway in size control of organ regeneration

2015 ◽  
Vol 57 (4) ◽  
pp. 341-351 ◽  
Author(s):  
Shinichi Hayashi ◽  
Hitoshi Yokoyama ◽  
Koji Tamura
Keyword(s):  
Signaling Pathway ◽  
Size Control ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Organ Regeneration

scholarly journals Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer

Cell Reports ◽  
2018 ◽  
Vol 25 (5) ◽  
pp. 1304-1317.e5 ◽  
Author(s):  
Yumeng Wang ◽  
Xiaoyan Xu ◽  
Dejan Maglic ◽  
Michael T. Dill ◽  
Kamalika Mojumdar ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Molecular Characterization ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

Energy restriction affect liver development in Hu sheep ram lambs through Hippo signaling pathway

2017 ◽  
Vol 49 (5) ◽  
pp. 603-611 ◽  
Author(s):  
Ting-Ting Zhang ◽  
Guo-Min Zhang ◽  
Yu-Hang Jin ◽  
Yi-Xuan Guo ◽  
Zhen Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Energy Restriction ◽  
Liver Development ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Ram Lambs ◽  
Hu Sheep

scholarly journals YAP Activation and Implications in Patients and a Mouse Model of Biliary Atresia

2021 ◽  
Vol 8 ◽  
Author(s):  
Chao Zheng ◽  
Jiaqian Luo ◽  
Yifan Yang ◽  
Rui Dong ◽  
Fa-Xing Yu ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Mouse Model ◽  
Biliary Atresia ◽  
Signaling Pathway ◽  
Target Genes ◽  
Hippo Signaling ◽  
Mice Model ◽  
Hippo Signaling Pathway ◽  
Ductal Cells

Background and Aim: Biliary atresia (BA), an inflammatory destruction of the bile ducts, leads to liver fibrosis in infants and accounts for half of cases undergoing pediatric liver transplantation. Yes-associated protein (YAP), an effector of the Hippo signaling pathway, is critical in maintaining identities of bile ductal cells. Here, we evaluated the expression of YAP and YAP target genes in BA livers and a rhesus rotavirus (RRV)-induced BA mice model.Methods: Liver specimens collected from 200 BA patients were compared with those of 30 non-BA patients. Model mice liver tissues were also collected. The expression of YAP and YAP target genes were measured by transfection, RNA-seq, immunohistochemistry, immunoblot, and quantitative PCR. Masson's trichrome staining and the Biliary Atresia Research Consortium (BARC) system were utilized to score liver fibrosis status.Results: The expression of YAP is elevated and positively correlated with fibrosis in BA livers. Moreover, ANKRD1, which is identified as the target gene of YAP, is also highly expressed in BA livers. Consistent with clinical data, YAP and ANKRD1 are significantly upregulated in RRV-induced BA mouse model.Conclusions: YAP expression is closely correlated with the bile duct hyperplasia and liver fibrosis, and may serve as an indicator for liver fibrosis and BA progression. This study indicates an involvement of the Hippo signaling pathway in the development of BA, and the YAP induced ANKRD1 expression may also be related to bile duct hyperplasia in BA. This provides a new direction for more in-depth exploration of the etiology and pathogenesis of biliary atresia.

Sign in / Sign up

Export Citation Format

Share Document