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Neurological and Mental Disorders
Published in Victor A. Bernstam, Pocket Guide to GENE LEVEL DIAGNOSTICS in Clinical Practice, 2019
An oncoprotein, designated Op18, has been described in acute lymphocytic leukemia and some solid tumors, including NB. This protein appears to be similar, if not identical, to the phosphoprotein prosolin, and another phosphoprotein called stathmin — all these proteins being related to the state of differentiation.
Regulation of Cell Functions
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
The functions of many intracellular or secreted proteins detected in proliferating cells are little understood. A proliferation-related cytosolic phosphoprotein, which is induced in lymphocytes following mitogenic stimulation, is represented by the 149-amino acid protein, oncoprotein 18 (Op-18), also called stathmin and prosolin.197 Op-18 may have a role in intracellular signal transduction and is expressed in markedly increased amounts in acute leukemia cells, which is due to increased RNA transcription from a structurally unaltered gene.
Diagnosis of endometrial receptivity and the embryo-endometrial dialog
Published in David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham, Textbook of Assisted Reproductive Techniques, 2017
Francisco Domínguez, Maria Ruiz-Alonso, Felipe Vilella, Carlos Simón
To develop a complete view of endometrial receptivity, we must advance beyond transcriptomics; indeed, proteomics should be considered the next step in the study of biological systems (48). Proteomic analyses reflect what is really happening in the tissue at the cellular level, and a global study of the proteomics of the endometrium will reveal the molecular changes that occur in the endometrium. Several attempts have been made to determine the proteomic patterns of the human endometrium. DeSouza et al. (49) employed the first quantitative approximation to assess the proteome using isotope-coded affinity tags, affinity purification, and liquid chromatography coupled online with mass spectrometry. Later, Parmar et al. (50) published a prospective study identifying proteins with differential expression throughout the menstrual cycle. Our group also investigated the proteomics of endometrial receptivity by comparing the pre-receptive versus the receptive human endometrium proteome (51). In this study, endometrial biopsies were obtained from the same fertile woman in the same menstrual cycle. Protein extracts were analyzed using two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The results show 32 differentially expressed proteins in the receptive versus the pre-receptive endometrium, highlighting two proteins, Annexin A2 and Stathmin 1 (52). These cytoskeleton-related proteins display consistent opposite regulation in the receptive versus the pre-receptive endometrium and seem to play important roles in acquiring endometrial receptivity. This finding is not surprising since the receptive phenotype is associated with the remodeling of epithelial organization, primarily as a result of the disruption of the cytoskeleton in response to hormones (32).
LASP2 inhibits trophoblast cell migration and invasion in preeclampsia through inactivation of the Wnt/β-catenin signaling pathway
Published in Journal of Receptors and Signal Transduction, 2021
Li Chen, Jing Wang, Xiaojun Fan, Yan Zhang, Mi Zhoua, Xiaohui Li, Lijuan Wang
Wnt signaling is an essential signal transduction pathway in the regulation of several biological processes, including cell proliferation, migration, invasion, and death [17]. The Wnt/β-catenin pathway is a canonical Wnt signaling pathway [18]. Wnt/β-catenin signaling has been demonstrated to participate in the development of multiple organ systems, such as skeletal, nervous, hematopoietic, cardiovascular, respiratory, digestive, and reproductive systems [17–19]. Increasing evidence denotes that abnormal activation of the Wnt/β-catenin pathway is involved in the pathogenesis of various human diseases, obstetrical, gynecological, and metabolic diseases, particularly in cancers [20,21]. Recent studies have demonstrated that the dysregulation of the Wnt/β-catenin signaling pathway is implicated in the pathogenesis of PE [11]. Wang et al. [22] reported that the mRNA and protein levels of Wnt1, β-catenin, c-myc, and cyclinD1 are significantly decreased in the severe preeclamptic placentas when compared with the control placentas, implying that Wnt/β-catenin signaling pathway may play a significant role in the pathogenesis of PE. Since Wnt signaling serves a crucial role in organ development, researchers have devoted to investigate the role of Wnt signaling in placental development. They found that Wnt signaling contributes to the development of the placenta [23–25]. Wnt signaling serves an essential role in the development, differentiation, and invasion of trophoblast cells [26]. A prior study reported that stathmin-1 directly regulates β-catenin translocation into the nucleus, which reduces MMP protein expression and inhibits trophoblast migration and invasion [27]. Therefore, abnormal activation of Wnt signaling may contribute to the process of PE through regulation of trophoblast cells.
Analysis of STMN2 CA repeats in italian ALS patients shows no association
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2023
Paolo Niccolò Doronzio, Serena Lattante, Giuseppe Marangi, Francesco Martello, Amelia Conte, Giulia Bisogni, Daniela Bernardo, Agata Katia Patanella, Emiliana Meleo, Marcella Zollino, Mario Sabatelli
Stathmin-2, a protein that promotes microtubule dynamics in axons, is thought to be implicated in ALS mechanisms (7–9). A reduced protein expression has been observed in ALS as consequence of the transcription of an early termination cryptic exon of Stathmin-2, resulting in truncated, nonfunctional mRNA. Loss of function of TDP-43 is assumed to cause this alteration of the splicing process (10).
Lipoplex-based therapeutics for effective oligonucleotide delivery: a compendious review
Published in Journal of Liposome Research, 2020
Pirthi Pal Singh, Veena Vithalapuram, Sunita Metre, Ravinder Kodipyaka
The overall progress in the establishment of GMP-quality and GMP-conformity of all of the ingredients and processes, successful application in pre-clinical trials with subsequent federal approval of the gene-transfer systems facilitate the entry of larger number of ONs in clinical trials. This section specifically gives insights on the lipoplex systems currently undergoing clinical trials with further details summarized in Table 3. These systems are mainly based on cationic lipids for systemic administration. Starting with the EWS/FLI1 fusion gene (Innovator-Gradali) universally designated as the dominant driver gene playing a key role in Ewing’s sarcoma (EWS, the second most frequently diagnosed primary malignant bone tumour in children) pathogenesis and maintenance. Here, the lipoplex is formed using DOTAP as the preferred cationic lipid. The plasmid-based Bi-shRNA EWS/FLI1 transcribes both siRNA and miRNA-like effectors each of which targets the identical type 1 translocation junction region of the EWS/FLI1-transcribed mRNA sequence. Target protein and RNA knockdown of 85–92% were demonstrated in-vitro in type 1 human EWS tumour cell lines with the optimal bi-shRNA EWS/FLI1 plasmid concentration. Type 1 EWS xenograft modelling confirmed dose-related safety and tumour response to pbi-shRNA EWS/FLI1 lipoplex (Rao et al.2016). As a parallel RNAi-based technology, Gradali also produced an expression Bi-shRNA construct specific for STMN1, which composed of dual stem–loop structures to simultaneously generate two functionally distinct effector small RNAs. Stathmin 1 is a 17-kDa phosphoprotein that is necessary for cell-cycle progression and mitosis. Stathmin 1 is highly expressed in a variety of assessed human cancers, including acute leukaemia, lymphoma, prostate cancer, breast cancer, head and neck cancer, and osteosarcoma, among others. Using the Bi-shRNA specific for STMN1 (pbi-shSTMN1), they have demonstrated effective STMN1 knockdown in human colorectal cancer (CCL-247) cells, achieving significant tumour cell killing and enhanced potency for a longer duration (Phadke et al.2011).