Facts and fiction: premalignant lesions of lung tissues

Klebe, Sonja; Henderson, Douglas W.

doi:10.1097/pat.0b013e32835f45fd

Cited by 30 publications

(24 citation statements)

References 71 publications

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“…[2][3][4] A lack of biomarkers for early diagnosis and prognostic markers is still one of the main challenges in NSCLC. 5 Therefore, the identification of new functional genes and characterization of the molecular mechanisms behind their involvement in NSCLC are essential for the development of specific diagnostic methods and the design of more individualized and effective therapeutic strategies for NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

et al. 2017

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Recently, the non-protein-coding functional elements in the human genome have been identified as key regulators in postgenomic biology, and a large number of pseudogenes as well as long non-coding RNAs (lncRNAs) have been found to be transcribed in multiple human cancers. However, only a small proportion of these pseudogenes has been functionally characterized. In this study, we screened for pseudogenes associated with human non-small-cell lung cancer (NSCLC) by comparative analysis of several independent datasets from the GEO. We identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for NSCLC patients. Knockdown of DUXAP8 impairs cell growth, migration, and invasion, and induces apoptosis both in vitro and in vivo. Mechanistically, DUXAP8 represses the tumor suppressors EGR1 and RHOB by recruiting histone demethylase LSD1 and histone methyltransferase EZH2, thereby promoting cell proliferation, migration, and invasion. These findings indicate that the pseudogene DUXAP8 may act as an oncogene in NSCLC by silencing EGR1 and RHOB transcription by binding with EZH2 and LSD1, which may offer a novel therapeutic target for this disease.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

et al. 2017

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“…A lung squamous cell carcinoma is typically preceded by squamous metaplasia with dysplasia in respiratory epithelium of the central airways (bronchi, etc. Sutherland and Berns, 2010; Kadara et al, 2012; Klebe and Henderson, 2013) and would be modeled by cultured bronchial epithelial cells (Xu et al, 2013; Stueckle et al, 2012). In fact, it has been proposed that different types of cancer stem cells may reside in different compartments of the lung (central or peripheral) and produce different types of cancers (i.e.…”

Section: Discussionmentioning

confidence: 99%

Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

Person

Ngalame

Makia

et al. 2015

Toxicology and Applied Pharmacology

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Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer.

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“…Patients at high risk for ISCC, such as smokers, are susceptible to focal squamous changes within the upper airway epithelia that are detectable by sensitive autofluorescence bronchoscopy techniques [4, 5]. The lesions of PSCC are usually small, do not disrupt the basement membrane and show a diverse histological spectrum that suggests a gradual morphological transformation of bronchial epithelia into low- and high-grade PSCC that eventually may progress into ISCC [6].…”

Section: Introductionmentioning

confidence: 99%

Whole Transcriptome Analysis of Pre-invasive and Invasive Early Squamous Lung Carcinoma in Archival Laser Microdissected Samples

Koper

Zeef

Joseph³

et al. 2017

Respir Res

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BackgroundPreinvasive squamous cell cancer (PSCC) are local transformations of bronchial epithelia that are frequently observed in current or former smokers. Their different grades and sizes suggest a continuum of dysplastic change with increasing severity, which may culminate in invasive squamous cell carcinoma (ISCC). As a consequence of the difficulty in isolating cancerous cells from biopsies, the molecular pathology that underlies their histological variability remains largely unknown.MethodTo address this issue, we have employed microdissection to isolate normal bronchial epithelia and cancerous cells from low- and high-grade PSCC and ISCC, from paraffin embedded (FFPE) biopsies and determined gene expression using Affymetric Human Exon 1.0 ST arrays. Tests for differential gene expression were performed using the Bioconductor package limma followed by functional analyses of differentially expressed genes in IPA.ResultsExamination of differential gene expression showed small differences between low- and high-grade PSCC but substantial changes between PSCC and ISCC samples (184 vs 1200 p-value <0.05, fc ±1.75). However, the majority of the differentially expressed PSCC genes (142 genes: 77%) were shared with those in ISCC samples. Pathway analysis showed that these shared genes are associated with DNA damage response, DNA/RNA metabolism and inflammation as major biological themes. Cluster analysis identified 12 distinct patterns of gene expression including progressive up or down-regulation across PSCC and ISCC. Pathway analysis of incrementally up-regulated genes revealed again significant enrichment of terms related to DNA damage response, DNA/RNA metabolism, inflammation, survival and proliferation. Altered expression of selected genes was confirmed using RT-PCR, as well as immunohistochemistry in an independent set of 45 ISCCs.ConclusionsGene expression profiles in PSCC and ISCC differ greatly in terms of numbers of genes with altered transcriptional activity. However, altered gene expression in PSCC affects canonical pathways and cellular and biological processes, such as inflammation and DNA damage response, which are highly consistent with hallmarks of cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0496-3) contains supplementary material, which is available to authorized users.

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Facts and fiction: premalignant lesions of lung tissues

Cited by 30 publications

References 71 publications

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

Whole Transcriptome Analysis of Pre-invasive and Invasive Early Squamous Lung Carcinoma in Archival Laser Microdissected Samples

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