Browsing by Subject "Hippo pathway"

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    MiR-22-3p regulates the proliferation, migration and invasion of colorectal cancer cells by directly targeting KDM3A through the Hippo pathway
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Jin, Rui-Ri; Zeng, Chunyan; Chen, Youxiang
    Colorectal cancer (CRC) has one of the highest incidences and mortality rates of all malignancies worldwide. microRNAs (miRNAs) have been reported to be involved in many biological processes of diseases. MiR-22-3p is considered to be involved in cancer progression, but its role in CRC remains unclear. In this study, we detected that in CRC, the level of miR-22-3p is downregulated. MiR-22-3p has antitumor effects in CRC. miR-22-3p can reduce the proliferative, invasive and migrative capacity of CRC cells. Luciferase reporter analyses confirmed that KDM3A was a target of miR-22-3p, which can directly target the 3’UTR of KDM3A and decrease the expression of KDM3A in CRC cells. Our study also confirmed that KDM3A plays a role as an oncogene in CRC. KDM3A overexpression attenuated the tumor suppressor effects of miR-22-3p in CRC cells, demonstrating that miR-22-3p exerts antitumor effects by targeting KDM3A. Overexpression of miR-22-3p in CRC reduced YAP1 expression, whereas overexpression of KDM3A restored the expression of YAP1. In summary, miR-22-3p might inhibit the progression of CRC by targeting KDM3A to regulate the HIPPO signaling pathway, which may provide an opportunity for the treatment of CRC.
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    The EP300/TP53 pathway, a suppressor of the Hippo and canonical WNT pathways, is activated in human hearts with arrhythmogenic cardiomyopathy in the absence of overt heart failure
    (Oxford University Press [University Publisher], 2021-06-14) Rouhi, Leila; Fan, Siyang; Cheedipudi, Sirisha M.; Braza Boils, Aitana; Sabater Molina, María; Yao, Yan; Robertson, Matthew J.; Coarfa, Cristian; Gimeno, Juan Ramón; Molina, Pilar; Gurha, Priyatansh; Zorio, Esther; Marian, Ali J.; Ciencias Sociosanitarias
    Aims Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease that typically manifests with cardiacarrhythmias, progressive heart failure, and sudden cardiac death (SCD). ACM is mainly caused by mutations ingenes encoding desmosome proteins. Desmosomes are cell–cell adhesion structures and hubs for mechanosensing and mechanotransduction. The objective was to identify the dysregulated molecular and biological pathways in human ACM in the absence of overt heart failure. Methods and results Transcriptomes in the right ventricular endomyocardial biopsy samples from three independent individuals carrying truncating mutations in the DSP gene and five control samples were analysed by RNA-Seq (discovery group). These cases presented with cardiac arrhythmias and had a normal right ventricular function. The RNA-Seq analysis identified 5000 differentially expressed genes (DEGs), which predicted suppression of the Hippo and canonical WNT pathways, among others. Dysregulated genes and pathways, identified by RNA-Seq, were tested for validation in the right and left ventricular tissues from five independent autopsy-confirmed ACM cases with defined mutations (validation group), who were victims of SCD and had no history of heart failure. Protein levels and nuclear localization of the cWNT and Hippo pathway transcriptional regulators were reduced in the right and left ventricular validation samples. In contrast, levels of acetyltransferase EP300, known to suppress the Hippo and canonical WNT pathways, were increased and its bona fide target TP53 was acetylated. RNA-Seq data identified apical junction, reflective of cell–cell attachment, as the most disrupted biological pathway, which were corroborated by disrupted desmosomes and intermediate filament structures. Moreover, the DEGs also predicted dysregulation of over a dozen canonical signal transduction pathways, including the Tec kinase and integrin signalling pathways. The changes were associated with increased apoptosis and fibro-adipogenesis in the ACM hearts.