scholarly journals Silencing Core Spliceosome Sm Gene Expression Induces a Cytotoxic Splicing Switch in the Proteasome Subunit Beta 3 mRNA in Non-Small Cell Lung Cancer Cells

2020 ◽  
Vol 21 (12) ◽  
pp. 4192 ◽  
Author(s):  
Maxime Blijlevens ◽  
Malgorzata A. Komor ◽  
Rocco Sciarrillo ◽  
Egbert F. Smit ◽  
Remond J. A. Fijneman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Alternative Splicing ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Fibroblasts ◽  
Clinical Samples ◽  
Small Cell Lung ◽  
Sm Proteins

The core spliceosomal Sm proteins were recently proposed as cancer-selective lethal targets in non-small cell lung cancer (NSCLC). In contrast, the loss of the commonly mutated cancer target SF3B1 appeared to be toxic to non-malignant cells as well. In the current study, the transcriptomes of A549 NSCLC cells, in which SF3B1 or SNRPD3 was silenced, were compared using RNA sequencing. The skipping of exon 4 of the proteasomal subunit beta type-3 (PSMB3) mRNA, resulting in a shorter PSMB3-S variant, occurred only after silencing SNRPD3. This observation was extended to the other six Sm genes. Remarkably, the alternative splicing of PSMB3 mRNA upon Sm gene silencing was not observed in non-malignant IMR-90 lung fibroblasts. Furthermore, PSMB3 was found to be overexpressed in NSCLC clinical samples and PSMB3 expression correlated with Sm gene expression. Moreover, a high PSMB3 expression corresponds to worse survival in patients with lung adenocarcinomas. Finally, silencing the canonical full-length PSMB3-L, but not the shorter PSMB3-S variant, was cytotoxic and was accompanied by a decrease in proteasomal activity. Together, silencing Sm genes, but not SF3B1, causes a cytotoxic alternative splicing switch in the PSMB3 mRNA in NSCLC cells only.

Integrative genomic and gene expression analysis of chromosome 7 identified novel oncogene loci in non-small cell lung cancer

Genome ◽  
2008 ◽  
Vol 51 (12) ◽  
pp. 1032-1039 ◽  
Author(s):  
Jennifer M. Campbell ◽  
William W. Lockwood ◽  
Timon P.H. Buys ◽  
Raj Chari ◽  
Bradley P. Coe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Chromosome 7 ◽  
Normal Lung ◽  
Clinical Samples ◽  
Small Cell Lung ◽  
Key Genes

Lung cancer accounts for over a quarter of cancer deaths, with non-small cell lung cancer (NSCLC) accounting for approximately 80% of cases. Several genome studies have been undertaken in both cell models of NSCLC and clinical samples to identify alterations underlying disease behaviour, and many have identified recurring aberrations of chromosome 7. The presence of recurring chromosome 7 alterations that do not span the well-studied oncogenes EGFR (at 7p11.2) and MET (at 7q31.2) has raised the hypothesis of additional genes on this chromosome that contribute to tumourigenesis. In this study, we demonstrated that multiple loci on chromosome 7 are indeed amplified in NSCLC, and through integrative analysis of gene dosage alterations and parallel gene expression changes, we identified new lung cancer oncogene candidates, including FTSJ2, NUDT1, TAF6, and POLR2J. Activation of these key genes was confirmed in panels of clinical lung tumour tissue as compared with matched normal lung tissue. The detection of gene activation in multiple cohorts of samples strongly supports the presence of key genes involved in lung cancer that are distinct from the EGFR and MET loci on chromosome 7.

Survival-Associated Alternative Splicing Signatures in Non-Small Cell Lung Cancer

2019 ◽  
Author(s):  
Deze Zhao ◽  
Chuantao Zhang ◽  
Yu Liang ◽  
Man Jiang ◽  
Li Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Alternative Splicing ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals RNA-Based Assay for Next-Generation Sequencing of Clinically Relevant Gene Fusions in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 139
Author(s):  
Caterina De Luca ◽  
Francesco Pepe ◽  
Antonino Iaccarino ◽  
Pasquale Pisapia ◽  
Luisella Righi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Limit Of Detection ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Clinical Samples ◽  
Gene Fusions ◽  
Small Cell Lung ◽  
Relevant Gene

Gene fusions represent novel predictive biomarkers for advanced non-small cell lung cancer (NSCLC). In this study, we validated a narrow NGS gene panel able to cover therapeutically-relevant gene fusions and splicing events in advanced-stage NSCLC patients. To this aim, we first assessed minimal complementary DNA (cDNA) input and the limit of detection (LoD) in different cell lines. Then, to evaluate the feasibility of applying our panel to routine clinical samples, we retrospectively selected archived lung adenocarcinoma histological and cytological (cell blocks) samples. Overall, our SiRe RNA fusion panel was able to detect all fusions and a splicing event harbored in a RNA pool diluted up to 2 ng/µL. It also successfully analyzed 46 (95.8%) out of 48 samples. Among these, 43 (93.5%) out of 46 samples reproduced the same results as those obtained with conventional techniques. Intriguingly, the three discordant results were confirmed by a CE-IVD automated real-time polymerase chain reaction (RT-PCR) analysis (Easy PGX platform, Diatech Pharmacogenetics, Jesi, Italy). Based on these findings, we conclude that our new SiRe RNA fusion panel is a valid and robust tool for the detection of clinically relevant gene fusions and splicing events in advanced NSCLC.

p53-regulated GML gene expression in non-small cell lung cancer: Relation to cisplatin chemosensitivity

Lung Cancer ◽  
2000 ◽  
Vol 29 (1) ◽  
pp. 193
Author(s):  
M Higashiyama ◽  
K Kodama ◽  
H Yokouchi ◽  
K Takami ◽  
Y Miyoshi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

Alternative splicing variants of carbonic anhydrase IX in human non-small cell lung cancer

Lung Cancer ◽  
2009 ◽  
Vol 64 (3) ◽  
pp. 271-276 ◽  
Author(s):  
Francesca Malentacchi ◽  
Lisa Simi ◽  
Caterina Nannelli ◽  
Matteo Andreani ◽  
Alberto Janni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Alternative Splicing ◽  
Carbonic Anhydrase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Carbonic Anhydrase Ix ◽  
Small Cell Lung ◽  
Splicing Variants

Effects of fine air particulates on gene expression in non-small-cell lung cancer

2017 ◽  
Vol 62 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Biao Yang ◽  
Xinming Li ◽  
Dongmei Chen ◽  
Chunling Xiao
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Cell-autonomous immune gene expression is repressed in pulmonary neuroendocrine cells and small cell lung cancer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ling Cai ◽  
Hongyu Liu ◽  
Fang Huang ◽  
Junya Fujimoto ◽  
Luc Girard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Neuroendocrine Cells ◽  
Immune Gene ◽  
Small Cell Lung ◽  
Immune Gene Expression ◽  
Pulmonary Neuroendocrine Cells

AbstractSmall cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed “variant” due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings may help guide the design of treatment regimens in SCLC.

scholarly journals Predicting Diagnostic Gene Biomarkers for Non-Small-Cell Lung Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Bin Liang ◽  
Yang Shao ◽  
Fei Long ◽  
Shu-Juan Jiang
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Association Network ◽  
Small Cell Lung ◽  
Functional Association ◽  
Functional Association Network ◽  
Gene Modules

Lung cancer is the primary reason for death due to cancer worldwide, and non-small-cell lung cancer (NSCLC) is the most common subtype of lung cancer. Most patients die from complications of NSCLC due to poor diagnosis. In this paper, we aimed to predict gene biomarkers that may be of use for diagnosis of NSCLC by integrating differential gene expression analysis with functional association network analysis. We first constructed an NSCLC-specific functional association network by combining gene expression correlation with functional association. Then, we applied a network partition algorithm to divide the network into gene modules and identify the most NSCLC-specific gene modules based on their differential expression pattern in between normal and NSCLC samples. Finally, from these modules, we identified genes that exhibited the most impact on the expression of their functionally associated genes in between normal and NSCLC samples and predicted them as NSCLC biomarkers. Literature review of the top predicted gene biomarkers suggested that most of them were already considered critical for development of NSCLC.

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