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https://www.readbyqxmd.com/read/28801591/new-variant-and-expression-studies-provide-further-insight-into-the-genotype-phenotype-correlation-in-yap1-related-developmental-eye-disorders
#1
R Holt, F Ceroni, D A Bax, S Broadgate, D Gold Diaz, C Santos, D Gerrelli, N K Ragge
YAP1, which encodes the Yes-associated protein 1, is part of the Hippo pathway involved in development, growth, repair and homeostasis. Nonsense YAP1 mutations have been shown to co-segregate with autosomal dominantly inherited coloboma. Therefore, we screened YAP1 for variants in a cohort of 258 undiagnosed UK patients with developmental eye disorders, including anophthalmia, microphthalmia and coloboma. We identified a novel 1 bp deletion in YAP1 in a boy with bilateral microphthalmia and bilateral chorioretinal coloboma...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796324/microrna-622-suppresses-the-proliferation-of-glioma-cells-by-targeting-yap1
#2
Jin Xu, Banyou Ma, Gong Chen, Dong Wei, Lixin Li, Weixing Hu
It has recently been shown that miR-622 plays a tumor suppressive role in many human cancers. However, the exact function and underlying mechanism are still unknown. Here, we reported that the level of miR-622 is clearly reduced in human glioma tissues in comparison with normal brain tissues and is negatively correlated with the histological grades. Additionally, ectopically expressed miR-622 significantly inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase in glioma cells. Furthermore, the bioinformatics analysis revealed that YAP1 possesses putative miR-622 -binding sites within its 3'UTR...
August 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28791365/fgf8-promotes-cell-proliferation-and-resistance-to-egfr-inhibitors-via-upregulation-of-egfr-in-human-hepatocellular-carcinoma-cells
#3
Yuanmin Pei, Xueling Sun, Xiwei Guo, Huashan Yin, Le Wang, Fugu Tian, Hongxi Jing, Xiaobo Liang, Jun Xu, Pengcheng Shi
Fibroblast growth factor 8 (FGF8), a member of the fibroblast growth factor (FGF) family, is upregulated in several human cancers, including HCC (HCC). Previous studies have demonstrated that FGF8 increased cell growth and invasion of tumor cells. In the present study we investigated whether FGF8 is involved in the cell proliferation and resistance to several drugs in human HCC cells. We stably overexpressed FGF8 by lentiviral transfection. In addition, we also added recombinant FGF8 instead of stably overexpressing FGF8 in human HCC cells...
August 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28782275/emerging-role-of-hippo-signalling-pathway-in-bladder-cancer
#4
REVIEW
Jianling Xia, Ming Zeng, Hua Zhu, Xiangjian Chen, Zhiliang Weng, Shi Li
Bladder cancer (BC) is one of the most common cancers worldwide with a high progression rate and poor prognosis. The Hippo signalling pathway is a conserved pathway that plays a crucial role in cellular proliferation, differentiation and apoptosis. Furthermore, dysregulation and/or malfunction of the Hippo pathway is common in various human tumours, including BC. In this review, an overview of the Hippo pathway in BC and other cancers is presented. We focus on recent data regarding the Hippo pathway, its network and the regulation of the downstream co-effectors YAP1/TAZ...
August 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28781952/network-analyses-elucidate-the-role-of-smyd3-in-esophageal-squamous-cell-carcinoma
#5
Xinning Liu, Zhoude Zheng, Chuhong Chen, Simin Guo, Zhennan Liao, Yue Li, Ying Zhu, Haiying Zou, Jianyi Wu, Wenming Xie, Pixian Zhang, Liyan Xu, Bingli Wu, Enmin Li
SMYD3 is a member of the SET and myeloid-Nervy-DEAF-1 (MYND) domain-containing protein family of methyltransferases, which are known to play critical roles in carcinogenesis. Expression of SMYD3 is elevated in various cancers, including esophageal squamous cell carcinoma (ESCC), and is correlated with the survival time of patients with ESCC. Here, we dissect gene expression data, from a previously described KYSE150 ESCC cell line in which SMYD3 had been knocked down, by integration with the protein-protein interaction (PPI) network, to find the new potential biological roles of SMYD3 and subsequent target genes...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28769563/delivery-of-mir-375-and-doxorubicin-hydrochloride-by-lipid-coated-hollow-mesoporous-silica-nanoparticles-to-overcome-multiple-drug-resistance-in-hepatocellular-carcinoma
#6
Huiying Xue, Zhaoyang Yu, Yong Liu, Weigang Yuan, Tan Yang, Jia You, Xingxing He, Robert J Lee, Lei Li, Chuanrui Xu
Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been shown that miR-375 inhibits P-gp expression via inhibition of astrocyte elevated gene-1 (AEG-1) expression in HCC, and induces apoptosis in HCC cells by targeting AEG-1 and YAP1. In this study, we prepared lipid-coated hollow mesoporous silica nanoparticles (LH) containing doxorubicin hydrochloride (DOX) and miR-375 (LHD/miR-375) to deliver the two agents into MDR HCC cells in vitro and in vivo...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28763902/-role-of-yes-associated-protein-1-in-angiotensin%C3%A2-induced-pulmonary-fibrosis-in-rats
#7
M X Pan, B B Zheng, N N Sun, Z M Zheng, Q J Yang, Y Meng
Objective: To explore the mechanism of Yes-associated protein 1 (Yap1) in angiotensinⅡ(AngⅡ)-induced pulmonary fibrosis. Methods:In vivo, 18 male Wistar rats were randomly divided into three equal groups with 6 rats in each group, including control group, bleomycin-treated group (BLM), and BLM+ AngⅡ group. 28 days later, the lung tissues in all groups were harvested for the HE and Masson staining as well as the immunohistochemical (IHC) staining for Yap1. In vitro, the isolated fibroblasts were treated with 10(-7) mmol/L AngⅡor the AngⅡ-targeted inhibitor irbesartan for the scheduled time for mRNA and protein expressions of Yap1, PDZ-binding motif (TAZ), and collagen Ⅰusing PCR and Western blot, as well as the translocation test from the nucleus to the cytoplasm of Yap1 and TAZ...
July 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28759040/tead1-4-exerts-oncogenic-role-and-is-negatively-regulated-by-mir-4269-in-gastric-tumorigenesis
#8
Y Zhou, T Huang, J Zhang, C C Wong, B Zhang, Y Dong, F Wu, J H M Tong, W K K Wu, A S L Cheng, J Yu, W Kang, K F To
TEA domain (TEAD) transcription factors are key components of the Hippo-YAP1 signaling pathway, but their functional role and regulatory mechanisms remain unclear. This study aims to comprehensively explore the expression pattern and functional role of TEAD family in gastric carcinogenesis and investigate its regulation by microRNAs (miRNAs). The mRNA and protein expression of TEAD family were examined by quantitative reverse transcription-PCR (qRT-PCR) and western blot. Their functional roles were determined by in vitro and in vivo studies...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28745364/expediting-dynamics-approach-to-understand-the-influence-of-14-3-3%C3%AE-causing-metastatic-cancer-through-the-interaction-of-yap1-and-%C3%AE-trcp
#9
Kamalesh D, Sriroopreddy Ramireddy, Raguraman P, Sudandiradoss C
The 14-3-3ζ protein acts as a molecular switch in regulating the TGF-β pathway, which alters from a tumor suppressor in the early stage of breast cancer to a promoter of metastasis in the late stage. This change is due to the binding of 14-3-3ζ with YAP1 and β-TRCP in premalignant and cancer cells, respectively. Owing to this inappropriate role of 14-3-3ζ when involved in cancer and metastasis, we predicted that Gln15, Glu17, Tyr211, and Gln219 are hotspot residues of 14-3-3ζ during its interaction with YAP1 protein...
July 26, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28733631/vgll4-selectively-represses-yap-dependent-gene-induction-and-tumorigenic-phenotypes-in-breast-cancer
#10
Yinglong Zhang, He Shen, Henry G Withers, Nuo Yang, Kayla E Denson, Ashley L Mussell, Alexander Truskinovsky, Qingyu Fan, Irwin H Gelman, Costa Frangou, Jianmin Zhang
Members of the mammalian Vestigial-like (VGLL) family of transcriptional cofactors activate genes in response to a wide variety of environmental cues. Recently, VGLL proteins have been proposed to regulate key signaling networks involved in cancer development and progression. However, the biological and clinical significance of VGLL dysregulation in human breast cancer pathogenesis remains unknown. Here, we report that diminished VGLL4 expression, but not VGLL1-3, correlated with both shorter relapse-free survival and shorter disease-specific survival of cancer patients with different molecular subtypes of breast cancer...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698296/prkci-promotes-immune-suppression-in-ovarian-cancer
#11
Sharmistha Sarkar, Christopher A Bristow, Prasenjit Dey, Kunal Rai, Ruth Perets, Alejandra Ramirez-Cardenas, Shruti Malasi, Emmet Huang-Hobbs, Monika Haemmerle, Sherry Y Wu, Michael McGuire, Alexei Protopopov, Shan Jiang, Joyce F Liu, Michelle S Hirsch, Qing Chang, Alexander J Lazar, Anil K Sood, Ronny Drapkin, Ronald DePinho, Giulio Draetta, Lynda Chin
A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring PRKC-ι (PRKCI). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called serous tubal intraepithelial carcinoma. Transgenic mouse studies establish PRKCI as an ovarian cancer-specific oncogene. Mechanistically, we show that the oncogenic activity of PRKCI relates in part to the up-regulation of TNFα to promote an immune-suppressive tumor microenvironment characterized by an abundance of myeloid-derived suppressor cells and inhibition of cytotoxic T-cell infiltration...
June 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28697132/overexpression-of-yes-associated-protein-1-an-independent-prognostic-marker-in-patients-with-pancreatic-ductal-adenocarcinoma-correlated-with-liver-metastasis-and-poor-prognosis
#12
Maria Teresa Salcedo Allende, Jorge Zeron-Medina, Javier Hernandez, Teresa Macarulla, Joaquim Balsells, Xavier Merino, Helena Allende, Josep Tabernero, Santiago Ramon Y Cajal Agüeras
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Overexpression of Yes associated protein 1 (YAP1), a downstream target of Hippo pathway, implicated in regulation of cell growth and apoptosis, has been reported in several human tumor types. The objective of this study was to investigate YAP1 expression in patients with PDAC and its prognostic values. METHODS: We evaluated YAP1 expression in 64 PDAC and 15 chronic pancreatitis (CP) cases and its related pancreatic intraepithelial neoplasia (PanIN) lesions and in 5 control subjects...
August 2017: Pancreas
https://www.readbyqxmd.com/read/28688217/yes-associated-protein-1-promotes-the-differentiation-and-mineralization-of-cementoblast
#13
Beining Yang, Hualing Sun, Fangfang Song, Yanru Wu, Jiawei Wang
Yes-associated protein 1 (YAP1) transcriptional coactivator is a mediator of mechanosensitive signaling. Cementum, which covers the tooth root surface, continuously senses external mechanical stimulation. Cementoblasts are responsible for the mineralization and maturation of the cementum. However, the effect of YAP1 on cementoblast differentiation remains largely unknown. In this study, we initially demonstrated that YAP1 overexpression enhanced the mineralization ability of cementoblasts. YAP1 upregulated the mRNA and protein expression of several cementogenesis markers, such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and dentin matrix acidic phosphoprotein 1 (DMP1)...
July 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28677785/microrna-345-inhibits-hepatocellular-carcinoma-metastasis-by-inhibiting-yap1
#14
Hui Zhang, Hui Liu, Huaqiang Bi
MicroRNAs (miRNAs) play critical roles in hepatocellular carcinoma (HCC). However, the expression and biological function of miR-345 in HCC remain unknown. The present study demonstrated that miR-345 expression was reduced in HCC tissues and cell lines. Decreased miR-345 expression was associated with unfavorable clinical features and poor prognosis. In vitro functional assays showed that miR-345 overexpression inhibited the migration and invasion of MHCC-97H cells while miR-345 knockdown promoted metastatic behavior of Hep3B cells...
June 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28677425/ikbke-promotes-glioblastoma-progression-by-establishing-the-regulatory-feedback-loop-of-ikbke-yap1-mir-let-7b-i
#15
Zhimeng Zhang, Jie Lu, Gaochao Guo, Yi Yang, Shicai Dong, Yang Liu, Yang Nan, Yue Zhong, Kai Yu, Qiang Huang
Recently, we have demonstrated that IKBKE (inhibitor of nuclear factor kappa-B kinase subunit epsilon) is overexpressed in human glioblastoma and that inhibition of IKBKE remarkably suppresses the proliferative and invasive behaviour of glioblastoma cells. However, the specific pathogenic molecular mechanism remains to be elucidated. In this study, we verified that IKBKE promotes YAP1 expression via posttranslational modification and accelerates YAP1 translocation to the nucleus for the development of glioblastoma...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28645247/the-correlation-between-poor-prognosis-and-increased-yes-associated-protein-1-expression-in-keratin-19-expressing-hepatocellular-carcinomas-and-cholangiocarcinomas
#16
KyuHo Lee, Kyoung-Bun Lee, Hae Yoen Jung, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh, Ja-June Jang
BACKGROUND: The Hippo pathway plays a vital role in liver regeneration and development by determining cellular lineage and regulating cell proliferation and apoptosis. In this study, we aimed to assess the role of the Hippo pathway in hepatic carcinogenesis and morphogenesis by examining Yes-associated protein 1 (YAP1) expression in the spectrum of hepatic carcinomas based on cellular lineage. METHODS: We examined 913 primary hepatic carcinomas, including hepatocellular carcinomas (HCCs), combined hepatocellular and cholangiocarcinomas (cHC-CCAs), intrahepatic cholangiocarcinomas (IHCCAs) and perihilar extrahepatic bile duct carcinomas (EHBCAs)...
June 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28628095/a-scaffold-protein-that-chaperones-a-cysteine-sulfenic-acid-in-h2o2-signaling
#17
Antoine Bersweiler, Benoît D'Autréaux, Hortense Mazon, Alexandre Kriznik, Gemma Belli, Agnès Delaunay-Moisan, Michel B Toledano, Sophie Rahuel-Clermont
In Saccharomyces cerevisiae, Yap1 regulates an H2O2-inducible transcriptional response that controls cellular H2O2 homeostasis. H2O2 activates Yap1 by oxidation through the intermediary of the thiol peroxidase Orp1. Upon reacting with H2O2, Orp1 catalytic cysteine oxidizes to a sulfenic acid, which then engages into either an intermolecular disulfide with Yap1, leading to Yap1 activation, or an intramolecular disulfide that commits the enzyme into its peroxidatic cycle. How the first of these two competing reactions, which is kinetically unfavorable, occurs was previously unknown...
June 19, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28627687/microrna%C3%A2-205-acts-as-a-tumor-suppressor-and-directly-targets-yap1-in-glioma
#18
Tao Ji, Xiejun Zhang, Weiping Li
Glioma is the most common form of primary malignant tumor that occurs in the central nervous system. The underlying molecular mechanism of the carcinogenesis and progression of glioma remains to be elucidated. It is well‑established that microRNAs (miRs) are associated with the regulation of glioma initiation and progression, and may represent a novel effective therapeutic strategy for the treatment of glioma. In the present study, the expression, roles and molecular mechanisms of miR‑205 in glioma were investigated...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28624413/srsf3-regulated-mir-132-212-controls-cell-migration-and-invasion-by-targeting-yap1
#19
Hye Ree Kim, Su Jin Hwang, Chang Hoon Shin, Kyung Hee Choi, Takbum Ohn, Hyeon Ho Kim
Although SRSF3 (Serine/arginine-rich splicing factor 3) plays a significant role in various biological processes, many of its functions still remain unclear. More particularly, little is known about SRSF3's involvement in the regulation of miRNA. In this report, we found that invasive and migratory abilities were inhibited in SRSF3-silenced U2OS and HeLa cells. We also found that a knockdown of SRSF3 results in a decreased expression level of REST (RE1-silencing transcription factor). The silencing of REST increased the expression of primary miR-132/212 as well as their mature forms...
June 14, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28624193/mir-375-and-doxorubicin-co-delivered-by-liposomes-for-combination-therapy-of-hepatocellular-carcinoma
#20
Yin-Ping Fan, Jia-Zhi Liao, Ya-Qi Lu, De-An Tian, Feng Ye, Peng-Xuan Zhao, Guang-Ya Xiang, Wang-Xian Tang, Xing-Xing He
Doxorubicin (DOX) is one of the most frequently used anti-cancer drugs and the front line option for hepatocellular carcinoma (HCC) treatment. However, the clinical applications of DOX are restricted largely due to its toxicity and chemoresistance. Here, we report that miR-375 and DOX were co-delivered by liposomes (named L-miR-375/DOX-NPs) for combination therapy of HCC and drug resistance reversion of DOX. In vitro, L-miR-375/DOX-NPs could deliver DOX and miR-375 efficiently and simultaneously into HCC cells and ensure the successful release of mature miR-375 and DOX...
June 16, 2017: Molecular Therapy. Nucleic Acids
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