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JOURNAL ARTICLE
Hyo Jin Kim, Yunsik Choi, Yuri Lee, Mi Hwangbo, Jongchan Kim
TEAD transcription factors play a central role in the Hippo signaling pathway. In this study, we focused on transcriptional enhancer factor TEF-3 (TEAD4), exploring its regulation by the deubiquitinase OTU domain-containing protein 6A (OTUD6A). We identified OTUD6A as a TEAD4-interacting deubiquitinase, positively influencing TEAD-driven transcription without altering TEAD4 stability. Structural analyses revealed specific interaction domains: the N-terminal domain of OTUD6A and the YAP-binding domain of TEAD4...
April 9, 2024: FEBS Letters
#42
JOURNAL ARTICLE
Neveen A Hussein, Samia A Ebid, Mohammad A Ahmad, Gamal E Khedr, Dina M Saad
MicroRNAs are small RNA molecules that have a significant role in translational repression and gene silencing through binding to downstream target mRNAs. MiR-762 can stimulate the proliferation and metastasis of various types of cancer. Hippo pathway is one of the pathways that regulate tissue development and carcinogenesis. Dysregulation of this pathway plays a vital role in the progression of cancer. This study aimed to evaluate the possible correlation between miR-762, the Hippo signaling pathway, TWIST1, and SMAD3 in patients with lung cancer, as well as patients with chronic inflammatory diseases...
April 8, 2024: Scientific Reports
#43
REVIEW
Fariba Dehghanian, Laleh Ebrahimi Ghahnavieh, Amirhossein Naghsh Nilchi, Sheyda Khalilian, Rezvan Joonbakhsh
The most significant factors that lead to cancer-related death in breast cancer (BC) patients include drug resistance, migration, invasion, and metastasis. Several signaling pathways are involved in the development of BC. The different types of BC are initially sensitive to chemotherapy, and drug resistance can occur through multiple molecular mechanisms. Regardless of developing targeted Therapy, due to the heterogenic nature and complexity of drug resistance, it is a major clinical challenge with the low survival rate in BC patients...
April 6, 2024: Gene
#44
JOURNAL ARTICLE
Zhan Zhang, Lili Chen, Qiao Yang, Xiaowan Tang, Jianhua Li, Guangwen Zhang, Youqun Wang, Hui Huang
Colon cancer has become a global public health challenge, and 5-Fluorouracil (5-FU) chemoresistance is a major obstacle in its treatment. Chemoresistance can be mediated by therapy-induced cellular senescence. This study intended to investigate mechanisms of INHBA (inhibin A) in 5-FU resistance mediated by cellular senescence in colon cancer. Bioinformatics analysis of INHBA expression in colon cancer tissues, survival analysis, and correlation analysis of cellular senescence markers were performed. The effects of INHBA on the biological characteristics and 5-FU resistance of colon cancer cells were examined through loss/gain-of-function and molecular assays...
April 6, 2024: International Journal of Biochemistry & Cell Biology
#45
REVIEW
Princy S Quadros-Mennella, Kurt M Lucin, Robin E White
Stroke, resulting in hypoxia and glucose deprivation, is a leading cause of death and disability worldwide. Presently, there are no treatments that reduce neuronal damage and preserve function aside from tissue plasminogen activator administration and rehabilitation therapy. Interestingly, Drosophila melanogaster , the common fruit fly, demonstrates robust hypoxic tolerance, characterized by minimal effects on survival and motor function following systemic hypoxia. Due to its organized brain, conserved neurotransmitter systems, and genetic similarity to humans and other mammals, uncovering the mechanisms of Drosophila's tolerance could be a promising approach for the development of new therapeutics...
2024: Frontiers in Cellular Neuroscience
#46
JOURNAL ARTICLE
Siyi Lin, Xinyu He, Ying Wang, Yu Chen, Aifu Lin
Cells within tissues are subject to various mechanical forces, including hydrostatic pressure, shear stress, compression, and tension. These mechanical stimuli can be converted into biochemical signals through mechanoreceptors or cytoskeleton-dependent response processes, shaping the microenvironment and maintaining cellular physiological balance. Several studies have demonstrated the roles of Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ) as mechanotransducers, exerting dynamic influence on cellular phenotypes including differentiation and disease pathogenesis...
April 15, 2024: Journal of Zhejiang University. Science. B
#47
JOURNAL ARTICLE
Minhao Yu, Yuan Shi, Yuan Gao, Yang Luo, Yihua Jin, Xiaoyi Liang, Zhuoran Tao, Guojun Zhu, Haiping Lin, Hao Li, Jun Qin, Zhijun Cao, Ming Zhong
Although anti-TNF antibodies are extensively used to treat Crohn's disease (CD), a significant proportion of patients, up to 40%, exhibit an inadequate response to this therapy. Our objective was to identify potential targets that could improve the effectiveness of anti-TNF therapy in CD. Through the integration and analysis of transcriptomic data from various CD databases, we found that the expression of AQP9 was significantly increased in anti-TNF therapy-resistant specimens. The response to anti-TNF therapy in the CD mouse model was significantly enhanced by specifically inhibiting AQP9...
April 5, 2024: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
#48
JOURNAL ARTICLE
Hongming Zheng, Honghai Wang, Yi Xu, Xu Xu, Zhenghuan Zhu, Jiawei Fang, Zhiwen Song, Jinbo Liu
Spinal cord injury (SCI) constitutes a significant clinical challenge, and there is extensive research focused on identifying molecular activities that can facilitate the repair of spinal cord injuries. Mammalian sterile 20-like kinase 2 (MST2), a core component of the Hippo signaling pathway, plays a key role in apoptosis and cell growth. However, its role in neurite outgrowth after spinal cord injury remains unknown. Through comprehensive in vitro and in vivo experiments, we demonstrated that MST2, predominantly expressed in neurons, actively participated in the natural development of the CNS...
April 6, 2024: Molecular Neurobiology
#49
JOURNAL ARTICLE
Kenji Namoto, Clara Baader, Vanessa Orsini, Alexandro Landshammer, Eva Breuer, Kieu Trinh Dinh, Rosemarie Ungricht, Monika Pikiolek, Stephane Laurent, Bo Lu, Alexandra Aebi, Katharina Schönberger, Eric Vangrevelinghe, Olivera Evrova, Tianliang Sun, Stefano Annunziato, Julie Lachal, Emily Redmond, Louis Wang, Kristie Wetzel, Paola Capodieci, Jonathan Turner, Gabi Schutzius, Vincent Unterreiner, Markus Trunzer, Nicole Buschmann, Dirk Behnke, Rainer Machauer, Clemens Scheufler, Christian N Parker, Magali Ferro, Armelle Grevot, Armin Beyerbach, Wei-Yu Lu, Stuart J Forbes, Jürgen Wagner, Tewis Bouwmeester, Jun Liu, Bindi Sohal, Sukhdeep Sahambi, Linda E Greenbaum, Felix Lohmann, Philipp Hoppe, Feng Cong, Andreas W Sailer, Heinz Ruffner, Ralf Glatthar, Bostjan Humar, Pierre-Alain Clavien, Michael T Dill, Elizabeth George, Jürgen Maibaum, Prisca Liberali, Jan S Tchorz
The YAP/Hippo pathway is an organ growth and size regulation rheostat safeguarding multiple tissue stem cell compartments. LATS kinases phosphorylate and thereby inactivate YAP, thus representing a potential direct drug target for promoting tissue regeneration. Here, we report the identification and characterization of the selective small-molecule LATS kinase inhibitor NIBR-LTSi. NIBR-LTSi activates YAP signaling, shows good oral bioavailability, and expands organoids derived from several mouse and human tissues...
April 4, 2024: Cell Stem Cell
#50
JOURNAL ARTICLE
Chenzhou Wu, Xiaomin Cai, Ying Wang, Carlos D Rodriguez, Giorgia Zoaldi, Lydia Herrmann, Chun-Yuh Huang, Xiaoqiong Wang, Viraj R Sanghvi, Rongze O Lu, Zhipeng Meng
The Hippo signaling is instrumental in regulating organ size, regeneration, and carcinogenesis. The cytoskeleton emerges as a primary Hippo signaling modulator. Its structural alterations in response to environmental and intrinsic stimuli control Hippo signaling pathway activity. However, the precise mechanisms underlying the cytoskeleton regulation of Hippo signaling are not fully understood. RAP2 GTPase is known to mediate the mechanoresponses of Hippo signaling via activating the core Hippo kinases LATS1/2 through MAP4Ks and MST1/2...
April 2, 2024: Journal of Biological Chemistry
#51
JOURNAL ARTICLE
Farnaz Roshanmehr, Shahriyar Abdoli, Zahra Bazi, Maryam Jari, Majid Shahbazi
CHO cells are extensively employed in biological drug industry to manufacture therapeutic proteins. Nevertheless, production of biopharmaceuticals faces obstacles such as limited growth and inadequate productivity. Employing host cell engineering techniques for CHO cells serves as a valuable approach to address the constraints encountered in biologics manufacturing. Despite advancements, most techniques focus on specific genes to address individual cellular challenges. The significance of YAP, transcriptional co-activator, cannot be overstated due to its involvement in regulating organ size and tumor formation...
April 4, 2024: Applied Microbiology and Biotechnology
#52
JOURNAL ARTICLE
Tianming Yu, Xiaomin Ma, Yang Cheng, Zeyu Wang, Guangyong Zhang, Huanxin Ding, Jialuo Yin, Yifei Wang, Sanyuan Hu
BACKGROUND: Sleeve gastrectomy (SG) is known to alleviate non-alcoholic fatty liver disease (NAFLD) and restore liver function; however, its underlying mechanism remains unclear. METHODS: We investigated the effect of SG on the metabolic phenotype of diet-induced obese (DIO) mice. Postoperative stained liver images were analyzed to determine the hepatocyte proliferation phenotype. Single-cell RNA sequencing was used to characterize the regeneration signals of the liver after SG in DIO mice, and qRT PCR was performed to verify the above results...
April 4, 2024: International Journal of Surgery
#53
JOURNAL ARTICLE
Rosane Mazzarella, Karina Cañón-Beltrán, Yulia N Cajas, Meriem Hamdi, Encina M González, Juliano C da Silveira, Claudia L V Leal, D Rizos
BACKGROUND: Extracellular vesicles (EVs) present in oviductal (OF) and uterine fluid (UF) have been shown to enhance bovine embryo quality during in vitro culture by reducing lipid contents and modulating lipid metabolism-related genes (LMGs), while also influencing cell proliferation, suggesting their involvement on the regulation of different biological pathways. The regulation of signaling pathways related to cell differentiation, proliferation, and metabolism is crucial for early embryo development and can determine the success or failure of the pregnancy...
April 4, 2024: Journal of Animal Science and Biotechnology
#54
JOURNAL ARTICLE
Hongpei Tan, Jiahao Liu, Yanan Li, Ze Mi, Baiying Liu, Pengfei Rong
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal cancers, and the molecular mechanisms underlying its progression are still not fully understood. The expression of CCDC25, a notably underexpressed gene in many tumors, has been understudied in ccRCC. This research aims to explore the role of CCDC25 in ccRCC's clinical outcomes and uncover the molecular pathways influenced by it. METHODS: A multi-tiered approach was adopted involving bioinformatic analysis, tissue sample evaluation, in vitro and in vivo experiments...
April 3, 2024: Cancer Cell International
#55
JOURNAL ARTICLE
Taasin Srivastava, Hung Nguyen, Gage Haden, Parham Diba, Steven Sowa, Norah LaNguyen, William Reed-Dustin, Wenbin Zhu, Xi Gong, Edward N Harris, Selva Baltan, Stephen A Back
Proteoglycans containing link-domains modify the extracellular matrix (ECM) to regulate cellular homeostasis and can also sensitize tissues/organs to injury and stress. Hypoxic-Ischemic (H-I) injury disrupts cellular homeostasis by activating inflammation and attenuating regeneration and repair pathways. In the brain, the main component of the ECM is the glycosaminoglycan (GAG), Hyaluronic Acid (HA), but whether HA modifications of the ECM regulate cellular homeostasis and response to H-I injury is not known...
April 3, 2024: Journal of Neuroscience
#56
JOURNAL ARTICLE
Jun Ji, Shuqi Xu, Xin Xu, Yuanzhuo Man, Lunguang Yao, Qingmei Xie, Yingzuo Bi
N6-methyladenosine (m6 A) methylation in transcripts has been suggested to influence tumorigenesis in liver tumors caused by the avian leukosis virus subgroup J (ALV-J). However, m6A modifications during ALV-J infection in vitro remain unclear. Herein, we performed m6A and RNA sequencing in ALV-J-infected chicken fibroblasts (DF-1). A total of 51 differentially expressed genes containing differentially methylated peaks were identified, which were markedly enriched in microRNAs (miRNAs) in cancer cells as well as apoptosis, mitophagy and autophagy, RNA degradation, and Hippo and MAPK signaling pathways...
March 19, 2024: Poultry Science
#57
JOURNAL ARTICLE
Lei Cao, Ruohui Han, Yingying Zhao, Xiaoyang Qin, Qian Li, Hui Xiong, Yu Kong, Ziyi Liu, Zexing Li, Feng Dong, Ting Li, Xiujuan Zhao, Lei Lei, Qian Zhao, Dayong Liu, Baofeng Wang, Xudong Wu
N(6)-methyladenosine (m6 A) critically regulates RNA dynamics in various biological processes. The m6 A demethylase ALKBH5 promotes tumorigenesis of glioblastoma, while the intricate web that orchestrates its regulation remains enigmatic. Here, we discover that cell density affects ALKBH5 subcellular localization and m6 A dynamics. Mechanistically, ALKBH5 is phosphorylated by the large tumor suppressor kinase 2 (LATS2), preventing its nuclear export and enhancing protein stability. Furthermore, phosphorylated ALKBH5 reciprocally erases m6 A from LATS2 mRNA, thereby stabilizing this transcript...
April 2, 2024: Cell Reports
#58
REVIEW
Akihiro Nita, Toshiro Moroishi
The Hippo pathway is a central regulator of tissue growth that has been widely studied in mammalian organ development, regeneration, and cancer biology. Although previous studies have convincingly revealed its cell-autonomous functions in controlling cell fate, such as cell proliferation, survival, and differentiation, accumulating evidence in recent years has revealed its non-cell-autonomous functions. This pathway regulates cell-cell communication through direct interactions, soluble factors, extracellular vesicles, and the extracellular matrix, providing a range of options for controlling diverse biological processes...
April 2, 2024: Inflammation and Regeneration
#59
JOURNAL ARTICLE
Julieta Ramírez-Cuéllar, Roberto Ferrari, Rosario T Sanz, Marta Valverde-Santiago, Judith García-García, A Silvina Nacht, David Castillo, Francois Le Dily, Maria Victoria Neguembor, Marco Malatesta, Sarah Bonnin, Marc A Marti-Renom, Miguel Beato, Guillermo P Vicent
The cancer epigenome has been studied in cells cultured in two-dimensional (2D) monolayers, but recent studies highlight the impact of the extracellular matrix and the three-dimensional (3D) environment on multiple cellular functions. Here, we report the physical, biochemical, and genomic differences between T47D breast cancer cells cultured in 2D and as 3D spheroids. Cells within 3D spheroids exhibit a rounder nucleus with less accessible, more compacted chromatin, as well as altered expression of ~2000 genes, the majority of which become repressed...
April 2, 2024: EMBO Journal
#60
JOURNAL ARTICLE
Oisun Jung, Min-Jeong Baek, Colin Wooldrik, Keith R Johnson, Kurt W Fisher, Jinchao Lou, Tanei J Ricks, Tianmu Wen, Michael D Best, Vincent L Cryns, Richard A Anderson, Suyong Choi
The Hippo pathway effectors Yes-associated protein 1 (YAP) and its homolog TAZ are transcriptional coactivators that control gene expression by binding to TEA domain (TEAD) family transcription factors. The YAP/TAZ-TEAD complex is a key regulator of cancer-specific transcriptional programs, which promote tumor progression in diverse types of cancer, including breast cancer. Despite intensive efforts, the YAP/TAZ-TEAD complex in cancer has remained largely undruggable due to an incomplete mechanistic understanding...
April 2, 2024: EMBO Journal
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