Long noncoding RNA LSINCT5 is up-regulated and related to progression in esophageal squamous cell carcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE128035 | GEO | 2022/03/07
REPOSITORIES: GEO
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Project description:CCAAT enhancer binding proteins (CEBPs) have critical roles in the physiological and pathological processes. However, the characteristics and contributions of CEBPs in esophageal squamous cell carcinoma (ESCC) is unknown. Here, we showed that most of CEBPs (including CEBPA, CEBPB, CEBPE, CEBPG, CEBPZ) were upregulated and amplified in ESCC. Of note, high CEBPG expression is a prognostic factor for the poor survival of patients with ESCC. Moreover, the ESCC specific transcription factor TP63 activates the expression of CEBPG by directly binding to its distal enhancer. Functionally, CEBPG significantly enhances the proliferation and migration of ESCC cells in vitro and in vivo. Mechanistically, CEBPG enhances the PI3K-AKT signaling pathways through directly binding to distal enhancer or/and promoter of downstream target genes, such as CCND1, MYC and CDK2 etc. These findings provide important characteristics and contributions insights into CEBPs dysregulation in ESCC and elucidate a crucial role for CEBPG in the progression of ESCC, which highlights its potential therapeutic target for patients.
2021-08-11 | GSE156257 | GEO
Project description:Background: Esophageal squamous cell carcinoma (ESCC) is a common invasive malignancy worldwide with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been reported to be involved in cancer development. However, lncRNAs that are functional in ESCC and the underlying molecular mechanisms remain largely unknown. Methods: Transcriptomic analysis was performed to identify dysregulated lncRNAs in ESCC tissue samples. The high expression of LINC00680 in ESCC was validated by RT-qPCR, and the oncogenic functions of LINC00680 was investigated by cell proliferation, colony formation, migration and invasion assays in ESCC cells in vitro and xenografts derived from ESCC cells in mice. RNA-seq, competitive endogenous RNA (ceRNA) network analysis, and luciferase reporter assays were carried out to identify LINC00680 target genes and the microRNAs (miRNAs) bound to LINC00680. Antisense oligonucleotides (ASOs) were used for in vivo treatment. Results: Transcriptome profiling revealed that a large number of lncRNAs was dysregulated in ESCC tissues. Notably, LINC00680 was highly expressed, and upregulation of LINC00680 was associated with large tumor size, advanced tumor stage, and poor prognosis. Functionally, knockdown of LINC00680 restrained ESCC cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, LINC00680 was found to act as a ceRNA by sponging miR-423-5p to regulate PAK6 (p21-activated kinase 6) expression in ESCC cells. The cell viability and motility inhibition induced by LINC00680 knockdown was significantly reversed upon PAK6 restoration and miR-423-5p inhibition. Furthermore, ASO targeting LINC00680 substantially suppressed ESCC both in vitro and in vivo. Conclusions: An oncogenic lncRNA, LINC00680, was identified in ESCC, which functions as a ceRNA by sponging miR-423-5p to promote PAK6 expression and ESCC. LINC00680/miR-423-5p/PAK6 axis may serve as promising diagnostic and prognostic biomarkers and therapeutic targets for ESCC.
2024-10-10 | GSE185617 | GEO
Project description:Esophageal cancer is one of the leading causes of cancer-related mortality because of poor prognosis. Long noncoding RNAs (lncRNAs) have been gradually demonstrated to play critical roles in cancer development. We identified a novel long noncoding RNA named linc00460 by microarray analysis using esophageal squamous cell carcinoma (ESCC) clinical samples, which has not been studied before. Our research indicated that linc00460 was overexpressed in the majority of tumor tissues and ESCC cell lines. Linc00460 expression was positively correlated with ESCC TNM stage, lymph node metastasis, and predicted poor prognosis. In vitro experiments showed that linc00460 depletion suppressed ESCC cell growth through regulating cell proliferation and cell cycle; in additional, linc00460 depletion accelerated ESCC cell apoptosis. We further revealed that linc00460 overexpression was manipulated by transcriptional co-activator CBP/P300 through histone acetylation. Given the high expression and important biological functions of linc00460, we suggest that linc00460 works as an oncogene and might be a valuable prognostic biomarker for ESCC diagnosis and treatment.
| S-EPMC5964888 | biostudies-literature
Project description:Long noncoding RNA LSINCT5 is up-regulated and related to progression in esophageal squamous cell carcinoma
| PRJNA526141 | ENA
Project description:Objective: Esophageal squamous carcinoma (ESCC) is one of the most common gastrointestinal tumors, and the PI3K/AKT signaling pathway plays a key role in the development of ESCC. circRNAs have been reported to be involved in the regulation of PI3K/AKT signaling, but the underlying mechanisms are unclear. This study aimed to identify protein-coding circRNAs and investigate their function in ESCC. Design: Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. A novel protein encoded by circ-PDE5A was identified by LC-MS/MS. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circ-PDE5A and its encoded PDE5A-500aa novel protein in ESCC. Construction of a nanoplatform for the coupling of circRNAs to investigate the therapeutic translation value of circ-PDE5A. Results: We found that circ-PDE5A expression was downregulated in ESCC cells and tissues, and its low expression was associated with later clinicopathological staging and poorer prognosis. Functionally, circ-PDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding the novel PDE5A-500aa protein, which was identified as a key player in regulating PI3K/AKT signaling activation in ESCC. Mechanistically, the novel PDE5A-500aa protein binds directly to PIK3IP1 and promotes USP14-mediated deubiquitination of the k48-linked polyubiquitin chain at residue K198 of PIK3IP1, thereby attenuating PI3K/AKT pathway in ESCC. In addition, the circ-PDE5A plasmid-coupled reduction-responsive nanoplatform successfully inhibited ESCC growth and metastasis. Conclusions: circ-PDE5A represents an epigenetic mechanism regulating PI3K/ATK signaling and serves as a novel and promising therapeutic target and prognostic marker for ESCC.
2024-01-15 | GSE250413 | GEO
Project description:The high recurrence rate and poor survival prospects of esophageal squamous cell carcinoma (ESCC) patients after treatment make the ongoing research on chemoprevention drugs for ESCC particularly important. In helping to solve this problem, we screened a large number of FDA-approved drugs and found that levodopa, a drug used to treat Parkinson’s disease, has an inhibitory effect on the growth of ESCC cells. To elucidate the molecular mechanisms, we applied mass spectrometry to investigate the anti-tumor activity of levodopa on ESCC. The results suggest that levodopa can down-regulate oxidative phosphorylation, non-alcoholic fatty liver disease (NAFLD) and parkinson disease pathways. SDHD, NDUFS4 and MT-CO3, major respiratory compounds in the mitochondria, were involved in these pathways. Down-regulation of these proteins is associated with mitochondrial dysfunction. Western blotting and immunofluorescence results confirmed the authenticity of proteomics data. Cell viability assay revealed that mitochondrial activity had been suppressed after levodopa treatment. Mitochondrial membrane potential reduction was detected by JC-1 and TMRE assays. And transmission electron microscope (TEM) analysis indicated that mitochondrial morphology changed. Taken together, levodopa inhibits the growth of ESCC through restraining the mitochondria.
2021-09-08 | PXD013824 | Pride
Project description:Esophageal squamous cell carcinoma (ESCC) is a heterogeneous cancer associated with high mortality rate. In India, it is the 6th most common cause of cancer-related mortality. In this study, we employed high-resolution mass spectrometry-based quantitative proteomics to characterize differential protein expression pattern associated with ESCC. We identified several differentially expressed proteins including PDPN, TOP2A, POSTN and MMP2 that were overexpressed in ESCC. In addition, we identified downregulation of esophagus tissue-enriched proteins such as SLURP1, PADI1, CSTA and small proline-rich proteins like SPRR3, SPRR2A, SPRR1A and CSTA, KRT4, KRT13 involved in squamous cell differentiation. We identified several overexpressed proteins belonging to 3q24-29 chromosomal region, corroborating CNV alterations in this region reported by several published studies. For example, we identified overexpression of SOX2, TP63, IGF2BP2 and RNF13 that are encoded by 3q26 region. Functional enrichment analysis revealed proteins involved in cell cycle pathways, DNA replication, spliceosome, and DNA repair pathways. We identified overexpression of multiple proteins that play a major role in alleviating ER stress. SYVN1/SEL1L complex forms the ER quality control machinery clearing misfolded proteins from ER. SYVN1 is an E3 ubiquitin ligase that ubiquitinates ER-resident proteins. There are also other non-canonical substrates of SYVN1 which are known to play a crucial role in tumor progression. Therefore, SYVN1 is a potential therapeutic target in ESCC.
2023-10-24 | PXD036238 | Pride
Project description:Twelve clinical samples from human esophageal squamous cell carcinoma (ESCC) (seven tumors and five non-tumors) were sequenced using Illumina high-throughput sequencing and the RNA-Seq profiling was investigated with 1730 genes significantly differentially expressed. The gene Rab25 was found to be down-regulated in tumors (p-value < 1E-20) and identified as a novel candidate tumor suppressor gene. The down-regulation of Rab25 was examined in a large cohort of ESCC and non-tumor cases by qPCR and immunohistochemistry analyses. Aberrant methylation in the promoter region of Rab25 was studied by demethylation treatment with 5-aza-dC and bisulfite genomic sequencing (BGS). In order to assess the effect of Rab25 on tumor growth and angiogenesis, in vitro and in vivo functional studies in ESCC cell lines using lentiviral-based overexpression or knockdown models were also performed. 7 tumor and 5 normal samples
2012-12-05 | E-GEOD-32424 | biostudies-arrayexpress
Project description:Inflammatory signals can promote tumorigenesis. The pro-inflammatory cytokine interleukin (IL)-1β is overexpressed in many types of tumor; however, it is unclear whether it directly interacted with oncogenes in esophageal squamous cell carcinoma. In this study, we performed RNA sequencing to identify tumorgenesis and recurrence-related factors in ESCC and identified FRAS1-related extracellular matrix protein (FREM)2 as a candidate oncogene. IL-1β and IL-1R1 were upregulated in ESCC tissue, which was accompanied by elevated Frem2 expression. FREM2 formed complex with IL-1R1 at the cell surface and promoted ESCC cell proliferation and migration via activation of nuclear factor-κB–p65/mitogen-activated protein kinase–c-Jun N-terminal kinase signaling. IL-1β stimulation resulted in the upregulation of FREM2 in ESCC cells through inhibition of Forkhead box P1. Increased FREM2 and IL-1R1 levels were correlated with shorter survival time in ESCC patients.
2019-09-03 | GSE119436 | GEO
Project description:Our aim is to identify frequent genomic aberrations both in ESCC and esophageal dysplasia, and to discover important copy number-driving genes and microRNAs in ESCC. We carried out array-based comparative genomic hybridization (array CGH) on 59 ESCC resection samples and 16 dysplasia biopsy samples. Expression of genes at 11q13.3 was analyzed by real-time PCR and immunohistochemistry (IHC). Integrated analysis was performed to identify genes or microRNAs with copy number-expression correlations. Two group experiment, esophageal dysplasia vs. esophageal squamous cell carcinoma. Biological replicates: 16 dysplasias vs. 59 carcinomas
2013-04-29 | E-GEOD-46452 | biostudies-arrayexpress