Cancer Signalling and Metabolism Group do Instituto de Investigação e Inovação em Saúde-i3s, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
Published: January 2024
AI Article Synopsis
Article Abstract
In a family with Familial Non-Medullary Thyroid Carcinoma (FNMTC), our investigation using Whole-Exome Sequencing (WES) uncovered a novel germline mutation []. USP42 is known for regulating p53, cell cycle arrest, and apoptosis, and for being reported as overexpressed in breast and gastric cancer patients. Recently, a missense mutation was described in FNMTC, suggesting a potential involvement in thyroid cancer. Aiming to explore the mutation as an underlying cause of FNMTC, our team validated the mutation in blood and tissue samples from the family. Using immunohistochemistry, the expression of USP42, Caspase-3, and p53 was assessed. The gene was silenced in human thyroid Nthy-Ori 3-1 cells using siRNAs. Subsequently, expression, viability, and morphological assays were conducted. p53, Cyclin D1, p21, and p27 proteins were evaluated by Western blot. USP42 protein was confirmed in all family members and was found to be overexpressed in tumor samples, along with an increased expression of p53 and cleaved Caspase-3. siRNA-mediated downregulation in Nthy-Ori 3-1 cells resulted in reduced cell viability, morphological changes, and modifications in cell cycle-related proteins. Our results suggest a pivotal role of mutation in thyroid cell biology, and this finding indicates that USP42 may serve as a new putative target in FNMTC.
Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
Objective: Endometrial cancer (EC) is the ninth most common malignancy among women. While mutations in JAK2 are frequently observed in EC, the specific biological functions of JAK2 in endometrial cancer are poorly understood.
Methods: The genetic alterations of JAK2 in different cancer types were explored using sequencing dataset deposited at TCGA database.
KCC2 is CNS neuron-specific chloride extruder, essential for the establishment and maintenance of the transmembrane chloride gradient, thereby enabling synaptic inhibition within the CNS. Herein, we highlight KCC2 hypofunction as a fundamental and conserved pathology contributing to neuronal circuit excitation/inhibition (E/I) imbalances that underly epilepsies, chronic pain, neuro-developmental/-traumatic/-degenerative/-psychiatric disorders. Indeed, downstream of both acquired and genetic factors, multiple pathologies (e.
Congenital hypothyroidism (CH) is a common neonatal endocrine disorder that is characterized by irreversible neurodevelopmental and growth retardation due to insufficient biosynthesis of thyroid hormones at birth. Determining the causative genetic variants in infants is important for neonatal management. It was aimed to evaluate the variant frequencies and spectrum of CH in the neonatal population of Foshan, China.
Wiskott-Aldrich syndrome (WAS) is a severe X-linked disorder caused by loss-of-function mutations in the WAS gene, responsible for encoding WASP, a key regulator of actin cytoskeleton in all hematopoietic cells except red blood cells. The mechanism underlying microthrombocytopenia, a distinctive feature of WAS and a major contributor to mortality, remains not fully elucidated. In this study, using different gene editing strategies, we corrected mutations in patient-derived WAS-induced pluripotent stem cell lines, generating isogeneic WAS iPSC lines.
The directional and sequential flow of cytokinin in plants is organized by a complex network of transporters. Genes involved in several aspects of cytokinin transport have been characterized; however, much of the elaborate system remains elusive. In this study, we used a transient expression system in tobacco (Nicotiana benthamiana) leaves to screen Arabidopsis (Arabidopsis thaliana) transporter genes and isolated ATP-BINDING CASSETTE TRANSPORTER C4 (ABCC4).
