b-catenin

Colorectal cancer (CRC) is a complex disease, determined by genetic, environmental and lifestyle-associated risk factors. Genetic (inherited) factors have great influence on its development; however, most cases of CRC are sporadic and gradually develop over several years. The main environmental risk factors are associated with b-catenin signaling pathway, including obesity, lack of physical activity, consumption of red and processed meats, alcoholism, and smoking. The pathway is related to cell homeostasis regulation and cell self-renewal during embryogenesis and adulthood...

We investigated the role of miR-150-5p in osteoarthritic (OA) chondrocytes, as well as the possible regulatory role of long non-coding RNAs (lncRNAs) in miR-150-5p expression. TargetScan, StarBase, DIANA-LncBase, and Open Targets databases were used to predict miR-150-5p target genes, lncRNAs/miR-150-5p interactions, and OA-related genes. Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Gene ontology (GO) and pathway analysis were performed using Enrichr database...

Epigenetic alterations have essential roles during colon adenocarcinoma (COAD) progression. As the coactivator of Wnt/b-catenin signaling, Pygopus 2 (Pygo2) binds H3K4me2/3 and participate in chromatin remodeling in multiple cancers. However, It remains unclear whether the Pygo2-H3K4me2/3 association has significance in COAD. We aimed to elucidate the roles of Pygo2 in COAD. Functionally, Pygo2 inhibition attenuated cell proliferation, self-renewal capacities in vitro. Pygo2 overexpression enhanced in vivo tumor growth...

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma having a poor overall survival that is in need for the development of new therapeutics. In this study, we report the identification and expression of a new isoform splice variant of the tyrosine kinase receptor AXL in MCL cells. This new AXL isoform, called AXL3, lacks the ligand-binding domain of the commonly described AXL splice variants and is constitutively activated in MCL cells. Interestingly, functional characterization of AXL3, using CRISPR inhibition, revealed that only the knock down of this isoform leads to apoptosis of MCL cells...

Various studies have recognized the vital role of the abnormal spindle microtubule assembly ( ASPM ) gene in the progression of numerous tumors and its association with their poorer clinical outcomes. Nonetheless, the clinical significance and regulatory mechanism of ASPM in papillary renal cell carcinoma (PRCC) have not been illuminated. Herein, we designed a series of experiments to determine the functional significance of ASPM in PRCC. The expression of ASPM was significantly elevated in PRCC tissues and cells, and a higher expression level of ASPM was associated with poor clinical outcomes in patients with PRCC...

BACKGROUND: Hepatocellular carcinoma (HCC) remains an aggressive malignancy with a poor prognosis and a leading cause of cancer-related mortality globally. Cumulative evidence suggests critical roles for endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in chronic liver diseases. However, the role of ER stress in HCC pathogenesis, aggressiveness and therapy response remains unclear and understudied. OBJECTIVES: Against this background, the present study evaluated the therapeutic efficacy and feasibility of notopterol (NOT), a furanocoumarin and principal component of Notopterygium incisum , in the modulation of ER stress and cancer stemness, and the subsequent effect on liver oncogenicity...

BACKGROUND: Type 2 diabetes is one of the most common metabolic diseases in recent years and has become an important risk factor for cardiovascular disorders. The first goal is to reduce type 2 diabetes, and in the case of cardiovascular disease, the second goal is to reduce and manage that disorder. MATERIALS AND METHODS: The rats were divided into 4 groups: Healthy Control (n=8), Diabetes Control (n=8), Diabetes Training (n=8), and Healthy Training (n=8). The protocol consisted of 8 weeks of High-intensity interval (5 sessions per week), where the training started with 80% of the peak speed in the first week, and 10% was added to this speed every week...

In human dystrophies, the progressive muscle wasting is exacerbated by ectopic deposition of fat and fibrous tissue originating from fibro/adipogenic progenitors (FAPs). In degenerating muscles, the ability of these cells to adjuvate a successful healing is attenuated and FAPs aberrantly expand and differentiate into adipocytes and fibroblasts. Thus, arresting the fibroadipogenic fate of FAPs, without affecting their physiological role, represents a valuable therapeutic strategy for patients affected by muscle diseases...

Signet-ring cell squamous cell carcinoma (SRCSCC) is an uncommon variant of cutaneous SCC that has been reported in the head and neck region. Herein, we present a case of a 56-year-old female with a cutaneous SCC that recurred after surgical excision, during treatment with cemiplimab (a programmed death receptor-1 (PD-1) inhibitor). Histologically, the recurrent SCC revealed a second component characterized by the presence of signet-ring-like cells (SRLCs). Immunohistochemical studies demonstrated that the tumor cells were positive for P63, CK5/6, CDX2, and P53 while negative for P16, CK7, CK20, and CD68 stains...

Kallistatin (KL) is a member of the serine proteinase inhibitor (serpin) family regulating oxidative stress, vascular relaxation, inflammation, angiogenesis, cell proliferation, and invasion. The heparin-binding site of Kallistatin has an important role in the interaction with LRP6 leading to the blockade of the Wnt signaling pathway. In this study, we aimed to explore the structural basis of the Kallistatin-LRP6E1E4 complex using in silico approaches and evaluating the anti-proliferative, apoptotic, and cell cycle arrest activities of Kallistatin in colon cancer lines...

BACKGROUND: The TMEM43/LUMA p.S358L mutation causes arrhythmogenic cardiomyopathy named as ARVC5, a fully penetrant disease with high risk of ventricular arrhythmias, sudden death and heart failure. Male gender and vigorous exercise independently predicted deleterious outcome. Our systems genetics analysis revealed importance of Tmem43 for cardiac and metabolic pathways associated with elevated lipid absorption from small intestine. This study sought to delineate gender specific cardiac, intestinal, and metabolic phenotypes in vivo and investigate underlying pathophysiological mechanisms of S358L mutation...

Osteosarcoma (OS) is one of the most common bone cancers that constantly affects children, teenagers, and young adults. Numerous epigenetic elements, such as miRNAs, have been shown to influence OS features like progression, initiation, angiogenesis, and treatment resistance. The expression of numerous genes implicated in OS pathogenesis might be regulated by miRNAs. This effect is ascribed to miRNAs' roles in the invasion, angiogenesis, metastasis, proliferation, cell cycle, and apoptosis. Important OS-related mechanistic networks like the WNT/b-catenin signaling, PTEN/AKT/mTOR axis, and KRAS mutations are also affected by miRNAs...

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays an important role in bladder carcinoma (BC) invasiveness and metastasis. Studies have shown that muscle-invasive BC (MIBC) and non-MIBC (NMIBC) are different at the molecular level owing to different EMT-related programming. Recent studies suggest that dysregulation of specific miRNAs is linked to EMT in BC. With this background, we aimed to study the immunoexpression of EMT-markers and its correlation with miRNA-200c expression in a series of MIBCs and NMIBCs...

Endometrial cancer is the most common gynecologic malignancy in the developed world. Risk stratification and treatment approaches are changing due to better understanding of tumor biology. Upregulated Wnt signaling plays an important role in cancer initiation and progression with promising potential for development of specific Wnt inhibitor therapy. One of the ways in which Wnt signaling contributes to progression of cancer, is by activating epithelial-to-mesenchymal transition (EMT) in tumor cells, causing the expression of mesenchymal markers, and enabling tumor cells to dissociate and migrate...

INTRODUCTION: Cancer Stem Cells (CSC) are responsible for maintaining tumor growth, chemoresistance, and metastasis. Therefore, understanding their characteristics is critical to progress in cancer therapy. While the contribution of the canonical Wnt/b-catenin signaling in both normal and CSCs had been well established, the function of non-canonical Wnt signaling cascades in stem cells is unclear. Recently, we reported that Wnt ligands trigger complex signaling in which the canonical and non-canonical responses can be simultaneously activated by one ligand in colon cancer cells, suggesting, therefore, that noncanonical Wnt pathways may also be important in CSCs...

Understanding prostate response to castration and androgen receptor signaling inhibitors (ARSI) is critical to improving long-term prostate cancer (PCa) patient survival. Here we use a multi-omics approach on 229,794 single cells to create a mouse single-cell reference atlas better suited to interpreting mouse prostate biology and castration response. Our reference atlas refines single-cell annotations and provides chromatin context, which, when coupled with mouse lineage tracing demonstrates that the castration-resistant luminal cells are distinct from the pre-existent urethra-proximal stem/progenitor cells...

The gaining popularity of tobacco and nicotine delivery products, such as electronic cigarettes (e-cigarettes) being perceived as relatively safe is of a medical concern. The long-term safety of these new products remains uncertain for oral health. In this study, in vitro effects of e-liquid were assessed in a panel of normal oral epithelium cell lines (NOE and HMK), oral squamous cell carcinoma (OSCC) human cell lines (CAL27 and HSC3), and a mouse oral cancer cell line (AT84) using cell proliferation, survival/cell death, and cell invasion assays...

LncRNA HOTAIR exhibited different effects in human cancers. However, the role of HOTAIR was not reported in osteosarcoma. This study aimed to explore the function of HOTAIR in osteosarcoma. Firstly, we examined HOTAIR expression in breast cancer tissues by the RT-qPCR assay and examined HOTAIR protein expression via immunocytochemistry, to chemical assay, and Western blot. Then, for further exploring the function of HOTAIR, we also examined it by CCK-8 and transwell assays. Downregulation of HOTAIR was detected in osteosarcoma, which predicted poor prognosis of patients with osteosarcoma...

Wnt-1 inducible signaling pathway protein 2 (WISP-2/CCN5) is a recently identified adipokine that has been described as an important mediator of canonical Wnt activation in adipogenic precursor cells. In osteoarthritis (OA), the most common form of arthritis, chondrocytes exhibit aberrant and increased production of pro-inflammatory mediators and matrix degrading enzymes such as IL-1β and MMP-13. Although recent evidence suggests a role for Wnt signaling in OA physiopathology, little is known about the involvement of WISP-2 in cartilage degradation...

Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies and is one of the major causes of cancer-related death. Over the last 15 years, the molecular landscape of HCC has been deciphered, with the identification of the main driver genes of liver carcinogenesis that belong to six major biological pathways, such as telomere maintenance, Wnt/b-catenin, P53/cell cycle regulation, oxidative stress, epigenetic modifiers, AKT/mTOR and MAP kinase. The combination of genetic and transcriptomic data composed various HCC subclasses strongly related to risk factors, pathological features and prognosis...