LPS-mediated noncoding RNA IFITM4P promotes malignant progression of oral leukoplakia through nucleocytoplasmic shuttling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE167292 | GEO | 2023/05/18
REPOSITORIES: GEO
Similar Datasets
Project description:LPS-mediated noncoding RNA IFITM4P promotes malignant progression of oral leukoplakia through nucleocytoplasmic shuttling
| PRJNA704081 | ENA
Project description:Oral leukoplakia (OL) is the most common premalignancy in the oral cavity. A small proportion of OLs progresses to oral squamous cell carcinoma (OSCC). To assess OSCC risk of OLs, we investigated the role of the transcriptional repressor enhancer of zeste homolog 2 (EZH2) in oral tumorigenesis and its clinical implication as an OSCC risk predictor. Immunohistochemistry was used to measure EZH2 expression in OLs from 76 patients, including 37 who later developed OSCC and 39 who did not. EZH2 expression was associated with clinicopathologic parameters and clinical outcomes. To determine the biological role of EZH2 in OL, EZH2 level was reduced using EZH2 siRNAs in Leuk-1 cells, its impact on cell cycle, anchorage-dependent/independent growth, and invasion was assessed. We observed strong EZH2 expression in 34 (45%), moderate expression in 26 (34%), and weak/no expression in 16 (21%) of the OLs. The higher EZH2 levels were strongly associated with dysplasia (P < 0.001) and OSCC development (P < 0.0001). Multivariate analysis indicated that EZH2 expression was the only independent factor for OSCC development (P < 0.0001). At 5 years after diagnosis, 80% of patients whose OLs expressed strong EZH2 developed OSCC whereas only 24% patients with moderate and none with weak/no EZH2 expression did so (P < 0.0001). In Leuk-1 cells, EZH2 downregulation resulted in G(1) arrest; decreased invasion capability, decreased anchorage-independent growth; downregulation of cyclin D1 and upregulation of p15(INK4B). Our data suggest that EZH2 plays an important role in OL malignant transformation and may be a biomarker in predicting OSCC development in patients with OLs.
| S-EPMC3677701 | biostudies-literature
Project description:The unsupervised hierarchical clustering analysis of the 122 miRNAs revealed a marked separation of mtOLK from OLK, suggesting that this differential expression profile might be used as a possible phenotypic discriminator between OLK and mtOLK.Comparing with OLK, 72 up-regulated and 50 down-regulated miRNAs were found in the mtOLK (p < 0.01) In the study presented here,20 OLK（OLK), 5 mtOLK（Ca） tissues and 5 normal mucousal tissues（N） were examined by miRNA array
2011-11-02 | E-GEOD-33299 | biostudies-arrayexpress
Project description:The unsupervised hierarchical clustering analysis of the 122 miRNAs revealed a marked separation of mtOLK from OLK, suggesting that this differential expression profile might be used as a possible phenotypic discriminator between OLK and mtOLK.Comparing with OLK, 72 up-regulated and 50 down-regulated miRNAs were found in the mtOLK (p < 0.01)
2011-11-02 | GSE33299 | GEO
Project description:BackgroundMost oral squamous cell carcinomas (OSCC) occur on the basis of oral leukoplakias (OLP). The histologic degree of dysplasia is insufficient for the prediction of OLP malignant transformation. Immunologic parameters are gaining importance for prognostic assessment and therapy of cancer. M2 polarized macrophages were shown to be associated with OSCC progression and inferior prognosis. The current study aims to answer the question if OLP with malignant transformation into OSCC within 5 years differ from OLP without transformation regarding macrophage infiltration and polarization.Methods201 specimens (50 transforming OLP, 53 non-transforming OLP, 49 corresponding OSCC and 49 healthy oral mucosa controls) were processed for immunohistochemistry. Samples were stained for CD68, CD163 and CD11c expression, completely digitalized and computer-assisted cell counting was performed. Epithelial and subepithelial compartments were differentially assessed. Groups were statistically compared using the Mann-Whitney U-test. A cut-off point for the discrimination of transforming and non-transforming OLP was determined and the association between macrophage infiltration and malignant transformation was calculated using the Chi-square test (χ2 test).ResultsMacrophage infiltration and M2 polarization in OLP with malignant transformation within 5 years was significantly increased compared to OLP without malignant transformation (p < 0.05). OSCC samples showed the highest macrophage infiltration and strongest M2 polarization (p < 0.05). Additionally, transforming OLP revealed a significant shift of macrophage infiltration towards the epithelial compartment (p < 0.05). χ2 test revealed a significant association of increased macrophage infiltration with malignant transformation (p < 0.05).ConclusionImmunological changes precede malignant transformation of OLP. Increased macrophage infiltration and M2 polarization was associated with the development of oral cancer in OLP. Macrophage infiltration could serve as predictive marker for malignant transformation.
| S-EPMC6945578 | biostudies-literature
Project description:BackgroundKey lncRNAs associated with the malignant progression of oral submucous fibrosis (OSF) to oral squamous cell carcinoma (OSCC) were identified.MethodsKey lncRNAs with sequential changes from normal oral mucosa (NOM) to OSF to OSCC were identified based on the GEO database. Kaplan-Meier analysis was used to screen lncRNAs related to OSCC prognosis. Cox regression analysis was used to validate the independent prognostic value. qPCR was used to confirm the expression of the candidate lncRNAs. Gene set enrichment analysis (GSEA), nucleocytoplasmic separation assay, fluorescence in situ hybridization, RNA knockdown, western blot, and cell viability assay were performed to investigate the biological functions of the candidate lncRNA. A nomogram was constructed to quantitatively predict OSCC prognosis based on TCGA.ResultsBioinformatics methods indicated that LINC02147 was sequentially downregulated from NOM to OSF to OSCC, as confirmed by clinical tissues and cells. Meanwhile, low LINC02147 expression, as an independent prognostic factor, predicted a poor prognosis for OSCC. GSEA and in vitro studies suggested that low LINC02147 expression promoted OSF malignant progression by promoting cell proliferation and differentiation. A LINC02147 signature-based nomogram successfully quantified each indicator's contribution to the overall survival of OSCC.ConclusionsLow LINC02147 expression promoted OSF malignant progression and predicted poor OSCC prognosis.
| S-EPMC9338683 | biostudies-literature
Project description:BackgroundThe optimal clinical management of oral precancer remains uncertain. We investigated the natural history of oral leukoplakia, the most common oral precancerous lesion, to estimate the relative and absolute risks of progression to cancer, the predictive accuracy of a clinician's decision to biopsy a leukoplakia vis-à-vis progression, and histopathologic predictors of progression.MethodsWe conducted a retrospective cohort study (1996-2012) of patients with oral leukoplakia (n = 4886), identified using electronic medical records within Kaiser Permanente Northern California. Among patients with leukoplakia who received a biopsy (n = 1888), we conducted a case-cohort study to investigate histopathologic predictors of progression. Analyses included indirect standardization and unweighted or weighted Cox regression.ResultsCompared with the overall Kaiser Permanente Northern California population, oral cancer incidence was substantially elevated in oral leukoplakia patients (standardized incidence ratio = 40.8, 95% confidence interval [CI] = 34.8 to 47.6; n = 161 cancers over 22 582 person-years). Biopsied leukoplakias had a higher oral cancer risk compared with those that were not biopsied (adjusted hazard ratio = 2.38, 95% CI = 1.73 to 3.28). However, to identify a prevalent or incident oral cancer, the biopsy decision had low sensitivity (59.6%), low specificity (62.1%), and moderate positive-predictive value (5.1%). Risk of progression to oral cancer statistically significantly increased with the grade of dysplasia; 5-year competing risk-adjusted absolute risks were: leukoplakia overall = 3.3%, 95% CI = 2.7% to 3.9%; no dysplasia = 2.2%, 95% CI = 1.5% to 3.1%; mild-dysplasia = 11.9%, 95% CI = 7.1% to 18.1%; moderate-dysplasia = 8.7%, 95% CI = 3.2% to 17.9%; and severe dysplasia = 32.2%, 95% CI = 8.1%-60.0%. Yet 39.6% of cancers arose from biopsied leukoplakias without dysplasia.ConclusionsThe modest accuracy of the decision to biopsy a leukoplakia vis-à-vis presence or eventual development of oral cancer highlights the need for routine biopsy of all leukoplakias regardless of visual or clinical impression. Leukoplakia patients, particularly those with dysplasia, need to be closely monitored for signs of early cancer.
| S-EPMC7566351 | biostudies-literature
Project description:Biological macromolecules are the basis of life activities. There is a separation of spatial dimension between DNA replication and RNA biogenesis, and protein synthesis, which is an interesting phenomenon. The former occurs in the cell nucleus, while the latter in the cytoplasm. The separation requires protein to transport across the nuclear envelope to realize a variety of biological functions. Nucleocytoplasmic transport of protein including import to the nucleus and export to the cytoplasm is a complicated process that requires involvement and interaction of many proteins. In recent years, many studies have found that proteins constantly shuttle between the cytoplasm and the nucleus. These shuttling proteins play a crucial role as transport carriers and signal transduction regulators within cells. In this review, we describe the mechanism of nucleocytoplasmic transport of shuttling proteins and summarize some important diseases related shuttling proteins.
| S-EPMC5983729 | biostudies-literature
Project description:Signal transducer and activator of transcription (STAT) proteins are transcription factors that in the latent state are located predominantly in the cytoplasm. Activation of STATs through phosphorylation of a single tyrosine residue results in nuclear translocation. The requirement of tyrosine phosphorylation for nuclear accumulation is shared by all STAT family members but mechanisms of nuclear translocation vary between different STATs. These differences offer opportunities for specific intervention. To achieve this, the molecular mechanisms of nucleocytoplasmic shuttling of STATs need to be understood in more detail. In this review we will give an overview on the various aspects of nucleocytoplasmic shuttling of latent and activated STATs with a special focus on STAT3 and STAT5. Potential targets for cancer treatment will be identified and discussed.
| S-EPMC6895884 | biostudies-literature
Project description:p21-activated kinase 5 (Pak5) is an effector for the small GTPase Cdc42, known to activate cell survival signaling pathways. Previously, we have shown that Pak5 localizes primarily to mitochondria. To study the relationship between Pak5 localization and its effects on apoptosis, we identified three N-terminal regions that regulate the localization of this kinase: a mitochondrial targeting sequence, a nuclear export sequence, and a nuclear localization sequence. When the first two sequences are deleted, Pak5 is retained in the nucleus and no longer protects cells from apoptosis. Moreover, blockade of nuclear export with leptomycin B causes endogenous Pak5 to accumulate in the nucleus. Additionally, the removal of the N-terminal nuclear localization sequence abolishes Pak5 translocation to the nucleus. Finally, we show that reduction of endogenous Pak5 expression in neuroblastoma and neural stem cells increases their sensitivity to apoptosis and that this effect is reversed upon reexpression of wild-type Pak5 but not of a mutant form of Pak5 that cannot localize to mitochondria. These results show that Pak5 shuttles from mitochondria to the nucleus and that the mitochondrial localization of Pak5 is vital to its effects on cell survival.
| S-EPMC1446938 | biostudies-literature