The RNA-binding protein SART3 promotes miR-34a biogenesis and G1 cell cycle arrest in lung cancer cells RNA

MicroRNAs (miRNAs or miRs) are small, noncoding RNAs that are implicated in the regulation of most biological processes. Global miRNA biogenesis is altered in many cancers, and RNA-binding proteins play a role in miRNA biogenesis, presenting a promising avenue for targeting miRNA dysregulation in diseases. miR-34a exhibits tumor-suppressive activities by targeting cell cycle regulators CDK4/6 and anti-apoptotic factor BCL-2, among other regulatory pathways such as Wnt, TGF-β, and Notch signaling. Many cancers exhibit down-regulation or loss of miR-34a, and synthetic miR-34a supplementation has been shown to inhibit tumor growth in vivo. However, the post-transcriptional mechanisms that cause miR-34a loss in cancer are not entirely understood. Here, using a proteomics-mediated approach in non-small-cell lung cancer (NSCLC) cells, we identified squamous cell carcinoma antigen recognized by T-cells 3 (SART3) as a putative pre-miR-34a–binding protein. SART3 is a spliceosome recycling factor and nuclear RNA-binding protein with no previously reported role in miRNA regulation. We found that SART3 binds pre-miR-34a with higher specificity than pre-let-7d (used as a negative control) and elucidated a new functional role for SART3 in NSCLC cells. SART3 overexpression increased miR-34a levels, down-regulated the miR-34a target genes CDK4/6, and caused a cell cycle arrest in the G1 phase. In vitro binding experiments revealed that the RNA-recognition motifs within the SART3 s...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Accelerated Communications Source Type: research

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AbstractPersonalised medicine for primary lung cancers (PLCs) requires molecular analysis of cancer tissue or cells. The primary objective of the present prospective study was to assess the concordance between epidermal growth factor receptor (EGFR) gene mutation detection and echinoderm microtubule-associated protein-like (EML) 4-anaplastic lymphoma kinase protein (ALK) expression using liquid-based cytology (LBC) samples and matched histology samples of PLC patients. A total of 117 patients who underwent surgical resection of non-small cell PLC were enrolled. Cytological specimens scratched from the resected PLC lesion w...
Source: Virchows Archiv - Category: Pathology Source Type: research
Abstract Autophagy, a highly conserved cellular proteolysis process, has been involved in non-small cell lung cancer (NSCLC). We tried to develop a prognostic prediction model for NSCLC patients based on the expression profiles of autophagy-associated genes. Univariate Cox regression analysis was used to determine autophagy-associated genes significantly correlated with overall survival (OS) of the TCGA lung cancer cohort. LASSO regression was performed to build multiple-gene prognostic signatures. We found that the 22-gene and 11-gene signatures could dichotomize patients with significantly different OS and indep...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
AbstractCancer treatment using immune checkpoint inhibitors is widely used, although biomarkers predictive of response are not well established. However, both the expressions of programmed cell death ligand 1 (PD-L1) and the tumor mutation burden (TMB) hold promise as such biomarkers for immune checkpoint inhibitors; however, its characteristics and clinical and immunological impacts have not been fully analyzed. We, therefore, evaluated the clinical and immunological parameters related to TMB to identify potential new biomarkers. We enrolled 92 patients with non-small-cell lung cancer who underwent surgery at Fukushima Me...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
In conclusion, the present study provides further understanding of the pathogenesis of LUSC, and reveals CCNB1, CEP55, FOXM1, MKI67 and TYMS as potential biomarkers or therapeutic targets. PMID: 31788059 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Venugopal N, Yeh J, Kodeboyina SK, Lee TJ, Sharma S, Patel N, Sharma A Abstract The discovery of lung carcinoma subtype-specific gene expression changes has the potential to elucidate the molecular differences and provide personalized therapeutic targets for these pathologies. The aim of the present study was to characterize the genetic profiles of the early stages (IA/IB) of two non-small cell lung cancer subtypes, adenocarcinoma (AD) and squamous cell carcinoma (SC). RNA-Seq gene expression data from The Cancer Genome Atlas was analyzed to compare the gene expression differences between AD and SC. The ge...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
AbstractPurposePrognostic significance of volumetric18F-fluorodeoxyglucose (FDG) positron emission tomography/computer tomography (PET/CT) parameters in carbon-ion radiotherapy (C-ion RT) treated stage I non-small cell lung cancer, and need of histology-wise separate cut-off values for risk stratification were assessed.MethodsThirty-nine patients (29 men and 10 women, 71.9 ± 8.3 years) who underwent FDG PET/CT examinations before C-ion RT were retrospectively evaluated. FDG-PET parameters: standardized uptake values (SUVmax, SUVpeak, and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and ...
Source: European Journal of Nuclear Medicine and Molecular Imaging - Category: Nuclear Medicine Source Type: research
Introduction: The relationship between lung cancer and COPD is well known. Recent clinical studies found a higher prevalence of obstructive sleep apnea (OSA) in patients suffering lung cancer. Although hypoxia has been suggested to be one of the main factors associated with lung malignancy, most studies addressing this topic have limitations due to the reduced number of patients recruited and because lung cancer has been analyzed avoiding its complexity in terms of different histotypes.Aim: to investigate the effect of different patterns of hypoxia on cells of the most prevalent histological sub-types of non-small cell lun...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Sleep and control of breathing Source Type: research
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Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Lung cancer Source Type: research
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Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Lung cancer Source Type: research
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Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Lung cancer Source Type: research
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