scholarly journals Functional annotation of extensively and divergently expressed miRNAs in suprachiasmatic nucleus of ClockΔ19 mutant mice

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yanli Wang ◽  
Ke Lv ◽  
Hailong Chen ◽  
Mei Zhao ◽  
Guohua Ji ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Signaling Pathway ◽  
Target Genes ◽  
Mutant Mice ◽  
Hippo Signaling ◽  
Time Points ◽  
Hippo Signaling Pathway ◽  
Mirnas Expression ◽  
Phase Amplitude

Circadian locomotor output cycles kaput protein (CLOCK) is a core transcription factor of complex integrated feedback loops in mammalian circadian clock. More genes have been reported to be regulated by CLOCK, however little is known about the role of CLOCK-mediated miRNAs. To dissect this, we used microarray analysis to measure miRNAs expression in suprachiasmatic nuclei (SCN) of wild-type (WT) and ClockΔ19 mutant mice at two different time points. We found that miRNAs regulation in two time points was extensive (nearly 75% of the miRNAs expressed at each time point), and very little overlap, with only six miRNAs in common. Besides this, the predicted CLOCK regulated miRNAs at two time points participated in extremely diverse pathways. We validated nine miRNAs (miR-125a-3p, miR-144, miR-199a-5p, miR-199b*, miR-200a, miR-200b, miR-203, miR-449a, and miR-96), which were involved in the same signaling pathway-hippo signaling pathway. The rhythms of these miRNAs showed a broad distribution of phase, amplitude, and waveform in Clock mutation. And further analysis indicated that there may be three models of miRNA-mediated circadian rhythms and hippo signaling pathway. MiRNA, the small player, may play a hub role in connecting circadian rhythms and other pathways via its multiple target genes networks.

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 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.

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

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 Interaction of the Hippo Pathway and Phosphatases in Tumorigenesis

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2438 ◽  
Author(s):  
Sahar Sarmasti Emami ◽  
Derek Zhang ◽  
Xiaolong Yang
Keyword(s):  
Signaling Pathway ◽  
Hippo Pathway ◽  
Underlying Mechanism ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Cellular Processes ◽  
Wide Range ◽  
Future Direction ◽  
The Hippo Pathway

The Hippo pathway is an emerging tumor suppressor signaling pathway involved in a wide range of cellular processes. Dysregulation of different components of the Hippo signaling pathway is associated with a number of diseases including cancer. Therefore, identification of the Hippo pathway regulators and the underlying mechanism of its regulation may be useful to uncover new therapeutics for cancer therapy. The Hippo signaling pathway includes a set of kinases that phosphorylate different proteins in order to phosphorylate and inactivate its main downstream effectors, YAP and TAZ. Thus, modulating phosphorylation and dephosphorylation of the Hippo components by kinases and phosphatases play critical roles in the regulation of the signaling pathway. While information regarding kinase regulation of the Hippo pathway is abundant, the role of phosphatases in regulating this pathway is just beginning to be understood. In this review, we summarize the most recent reports on the interaction of phosphatases and the Hippo pathway in tumorigenesis. We have also introduced challenges in clarifying the role of phosphatases in the Hippo pathway and future direction of crosstalk between phosphatases and the Hippo pathway.

Regulatory role of microRNAs in cancer through Hippo signaling pathway

2020 ◽  
Vol 216 (12) ◽  
pp. 153241 ◽  
Author(s):  
Reza Vaezi Astamal ◽  
Asma Maghoul ◽  
Sina Taefehshokr ◽  
Taha Bagheri ◽  
Ehsan Mikaeili ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Regulatory Role ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

scholarly journals The role of Hippo signaling pathway in physiological cardiac hypertrophy

Bioimpacts ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 251-257
Author(s):  
Majid Gholipour ◽  
Arezoo Tabrizi
Keyword(s):  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Exercise Group ◽  
Expression Level ◽  
Control Group ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Physiological Cardiac Hypertrophy

Introduction: The role of Hippo signaling pathway, which was identified by genetic studies as a key regulator for tissue growth and organ size, in promoting physiological cardiac hypertrophy has not been investigated. Methods: Fourteen male Wistar rats were randomly assigned to the exercise and control groups. The exercise group ran 1 hour per day, 5 days/week, at about 65%-75% VO2max on the motor-driven treadmill with 15º slope, and the control group ran 15 min/d, 2 days/week at 9 m/min (0º inclination), throughout the eight-week experimental period. Forty-eight hours after the last session, hearts were dissected and left ventricles were weighed and stored for subsequent RT-PCR analysis. Results: Despite a significant increase in the MAP4k1 expression levels in the exercise group (P = 0.001), the Mst1 expression was inhibited compared to the control group (P < 0.001) which was followed by suppression of Lats1 expression (P = 0.001). Compared with the control group, significant increases were observed in heart weight/body weight (P = 0.024) and left ventricular weight/body weight (P = 0.034) ratios in the exercise group. The H&E staining confirmed the cardiac hypertrophy that may be partly due to a significant increase in Yap1 expression level compared with the control group (P<0.001), which was confirmed by Western blot analysis. Conclusion: Increased MAP4K1 expression did not influence Lats1 activation. The exercise training protocol suppressed Mst1 and Lats1 (Hippo pathway) and caused an increase in Yap1 expression level, which led to physiological cardiac hypertrophy in healthy rats. Further studies are suggested to apply this exercise protocol for the prevention and/or rehabilitation of cardiovascular disease and health promotion.

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