Notch-regulated ankyrin-repeat protein (NRARP) has recently been reported to be involved in a number of malignant cancers; however, its role in non-small lung cancer (NSCLC) remains unclear. The present study aimed to identify whether NRARP could be applied as a novel prognostic marker for NSCLC. A total of 108 NSCLC patients were enrolled in the present study and their lung tissues were collected. Reverse-transcription quantitative polymerase chain reaction and immunohistochemical staining were used to assess the mRNA and protein levels of NRARP. Appropriate statistical tests were performed to evaluate the associations between NRARP protein expression and clinicopathological features and prognosis in NSCLC patients. The results revealed that NRARP expression was significantly associated with tumor differentiation (P=0.001), Tumor-Node-Metastasis stage (P=0.004) and cigarette smoking (P0.001). Furthermore, patients with higher NRARP protein expression had significantly shorter overall survival times (P<0.001). Multivariate analysis indicated that overexpression of NRARP protein could be applied as an independent prognostic biomarker for NSCLC. In summary, the present study demonstrated that NRARP protein is overexpressed in NSCLC and that high NRARP expression is correlated with tumor progression and overall survival time. These data indicated the potential value of NRARP as a novel therapeutic target for the treatment of NSCLC.
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http://dx.doi.org/10.3892/ol.2018.8826 | DOI Listing |
Chem Biol Drug Des
September 2022
Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
The Notch-regulated ankyrin repeat protein (NRARP) functions as a molecular link between Notch and Wnt signaling pathways. Although it has recently been identified to be overexpressed in breast cancer (BC), the molecular mechanisms that regulate NRARP remain unknown. Since microRNAs (miRNAs) regulate gene expression post-transcriptionally, miRNA dysregulation could explain the abnormal gene expression.
View Article and Find Full Text PDFComput Struct Biotechnol J
May 2022
Faculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760, České Budějovice 370 05, Czech Republic.
Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible for such differences has not been fully described yet. Thus, we performed a comprehensive analysis of alterations in host poly-(A)/miRNA/lncRNA expression upon TBEV infection in human primary neurons (high cytopathic effect) and astrocytes (low cytopathic effect).
View Article and Find Full Text PDFSci Signal
November 2019
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Canonical Notch signaling relies on regulated proteolysis of the receptor Notch to generate a nuclear effector that induces the transcription of Notch-responsive genes. In higher organisms, one Notch-responsive gene that is activated in many different cell types encodes the Notch-regulated ankyrin repeat protein (NRARP), which acts as a negative feedback regulator of Notch responses. Here, we showed that NRARP inhibited the growth of Notch-dependent T cell acute lymphoblastic leukemia (T-ALL) cell lines and bound directly to the core Notch transcriptional activation complex (NTC), requiring both the transcription factor RBPJ and the Notch intracellular domain (NICD), but not Mastermind-like proteins or DNA.
View Article and Find Full Text PDFJ Endocrinol
June 2019
Division of Endocrinology and Centre for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Lucknow, India.
miRNAs have appeared as critical controllers of gene expression at post-transcriptional level either by degrading RNA transcripts or repressing translation. It is evident from the ever-growing scientific literature that miRNAs play a significant role in osteoblast commitment and differentiation. Here, we report that overexpression of miR-487b-3p leads to inhibition of osteoblastic differentiation.
View Article and Find Full Text PDFAnn Oncol
September 2018
Early Clinical Drug Development Group, Vall d´Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain.
Background: Deregulated Notch signaling due to mutation or overexpression of ligands and/or receptors is implicated in various human malignancies. γ-Secretase inhibitors inhibit Notch signaling by preventing cleavage of transmembrane domain of Notch protein. LY3039478 is a novel, potent Notch inhibitor decreases Notch signaling and its downstream biologic effects.
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