Browse
Submit Data
Databases
API
Help

Dataset Information

18 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long non-coding RNA ELDR enhances oral cancer growth by promoting ILF3-cyclin E1 signaling.

ABSTRACT: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer with a 5-year overall survival rate of 50%. Thus, there is a critical need to understand the disease process, and to identify improved therapeutic strategies. Previously, we found the long non-coding RNA (lncRNA) EGFR long non-coding downstream RNA (ELDR) induced in a mouse tongue cancer model; however, its functional role in human oral cancer remained unknown. Here, we show that ELDR is highly expressed in OSCC patient samples and in cell lines. Overexpression of ELDR in normal non-tumorigenic oral keratinocytes induces cell proliferation, colony formation, and PCNA expression. We also show that ELDR depletion reduces OSCC cell proliferation and PCNA expression. Proteomics data identifies the RNA binding protein ILF3 as an interacting partner of ELDR. We further show that the ELDR-ILF3 axis regulates Cyclin E1 expression and phosphorylation of the retinoblastoma (RB) protein. Intratumoral injection of ELDR-specific siRNA reduces OSCC and PDX tumor growth in mice. These findings provide molecular insight into the role of ELDR in oral cancer and demonstrate that targeting ELDR has promising therapeutic potential.

SUBMITTER: Sur S

PROVIDER: S-EPMC7726807 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Long non-coding RNA ELDR enhances oral cancer growth by promoting ILF3-cyclin E1 signaling

Project description:Oral squamous cell carcinoma (OSCC) is the sixth most common cancer with a five-year overall survival rate of 50%. Thus, there is a critical need to understand the disease process, and to identify improved therapeutic strategies. Previously, we found the conserved long non-coding RNA (lncRNA) ELDR induced in a mouse tongue cancer model, however its functional role in human oral cancer remained unknown. Here, we show that ELDR is highly expressed in OSCC patient samples and in cell lines. Overexpression of ELDR in normal non-tumorigenic oral keratinocytes induces cell proliferation, colony formation and PCNA expression. We also show that ELDR depletion reduces OSCC cell proliferation and PCNA expression. Proteomics data identify the RNA binding protein ILF3 as an interacting partner of ELDR. We further show that the ELDR-ILF3 axis regulates Cyclin E1 expression and phosphorylation of the retinoblastoma (RB) protein. Intratumoral injection of ELDR-specific siRNA reduces OSCC and PDX tumor growth in mice. These findings provide molecular insight into the role of ELDR in oral cancer and demonstrate that targeting ELDR has promising therapeutic potential.

| S-SCDT-EMBOR-2020-51042V1P | biostudies-other

The long non-coding RNA LOC441204 enhances cell growth in human glioma.

Project description:Glioma is the most common and aggressive type of brain tumor. While long non-coding RNAs (lncRNAs) are clearly more abundant in human brain than protein-coding genes, the specific roles of lncRNAs and mechanisms underlying their dysregulation in glioma remain unclear. Here, we focused on lncRNAs that are differentially expressed in brain tumor and their potential biological functions. LOC441204, a novel non-coding RNA gene displaying high expression in clinical specimens of brain tumor and significant upregulation in glioma cell lines in microarray analyses, was selected for further study. Notably, knockdown of LOC441204 suppressed tumor cell proliferation in two glioma cell lines. Moreover, LOC441204-induced tumor cell growth was mediated the stabilization of ?-catenin pathway. Briefly, LOC441204 bound to ?-catenin preventing its degradation, resulting in downstream p21 repression and cdk4 activation to enhance glioma cell proliferation. Collectively, our findings indicate a pro-oncogenic role of LOC441204 in tumor cell growth through activation of the ?-catenin/p21/cdk4 cascade to act as a potential diagnostic marker or therapeutic target in brain tumor.

| S-EPMC5514141 | biostudies-other

The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex.

Project description:BackgroundAs a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown.MethodsWe identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR.ResultsFunctionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation.ConclusionOur findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.

| S-EPMC7846991 | biostudies-literature

Profiling long non-coding RNA expression in oral premalignant lesions

Project description:Oral epithelial dysplasias are believed to progress through a series of histopathological stages; from mild to severe dysplasia, to carcinoma in situ, and finally to invasive OSCC. Underlying this change in histopathological grade are gross chromosome alterations and changes in gene expression of both protein-coding genes and non-coding RNAs. Recent papers have described associations of aberrant expression of microRNAs, one class of non-coding RNAs, with oral cancer. However, expression profiling of long non-coding RNAs (lncRNAs) has not been reported. Long non-coding RNAs are a novel class of mRNA-like transcripts with no protein coding capacity, but with a variety of functions including roles in epigenetics and gene regulation. In recent reports, the aberrant expression of lncRNAs has been associated with human cancers, suggesting a critical role in tumorigenesis. Here, we present the first long non-coding RNA expression map for the human oral mucosa. We describe the expression of 325 long non-coding RNAs, suggesting lncRNA expression contributes significantly to the oral transcriptome. Intriguingly, 60% of the detected lncRNAs show aberrant expression in oral premalignant lesions. A number of these lncRNAs have been previously associated with other human cancers. A total of six normal oral samples and ten oral premalignant lesions were used to construct SAGE libraries which were then queried for long non-coding RNA expression profiles. The six normal oral samples were previously deposited as GSE8127.

| S-ECPF-GEOD-31021 | biostudies-other

DDX3 regulates cell growth through translational control of cyclin E1.

Project description:DDX3 belongs to the DEAD box family of RNA helicases, but the details of its biological function remain largely unclear. Here we show that knockdown of DDX3 expression impedes G(1)/S-phase transition of the cell cycle. To know how DDX3 may act in cell cycle control, we screened for cellular mRNA targets of DDX3. Many of the identified DDX3 targets encoded cell cycle regulators, including G(1)/S-specific cyclin E1. DDX3 depletion specifically downregulates translation of cyclin E1 mRNA. Moreover, our data suggest that DDX3 participates in translation initiation of targeted mRNAs as well as in cell growth control via its RNA helicase activity. Consistent with these findings, we show that in the temperature-sensitive DDX3 mutant hamster cell line tsET24, cyclin E1 expression is downregulated at a nonpermissive temperature that inactivates mutant DDX3. Taken together, our results indicate that DDX3 is critical for translation of cyclin E1 mRNA, which provides an alternative mechanism for regulating cyclin E1 expression during the cell cycle.

| S-EPMC2976371 | biostudies-literature

Long non?coding RNA CCAT1 enhances human non?small cell lung cancer growth through downregulation of microRNA?218.

Project description:Long non?coding RNAs (lncRNAs) have critical functions in non?small cell lung cancer (NSCLC) growth. In the present study, we showed that lncRNA?CCAT1 was upregulated in NSCLC tissues. High expression of lncRNA?CCAT1 was related to tumor growth and reduced survival rate. We used short hairpin RNAs (shRNAs) to inhibit the expression of lncRNA?CCAT1 in NSCLC cells. In vitro and in vivo results demonstrated that lncRNA?CCAT1 knockdown suppressed tumor proliferation and induced apoptosis. Furthermore, microRNA?218 (miR?218) was confirmed as an effective target of lncRNA?CCAT1 in NSCLC. B lymphoma Mo?MLV insertion region 1 homolog (BMI?1), which served as a downstream target of miR?218, was also inhibited by lncRNA?CCAT1 knockdown. In conclusion, the present study indicated that upregulation of lncRNA?CCAT1 in NSCLC is associated with tumor malignant potential. lncRNA?CCAT1 enhances tumor growth in NSCLC by directly inhibiting miR?218 and indirectly increasing BMI?1 expression.

| S-EPMC7057767 | biostudies-literature

Overexpression of YBX1 Promotes Pancreatic Ductal Adenocarcinoma Growth via the GSK3B/Cyclin D1/Cyclin E1 Pathway.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers due to frequently late diagnosis and futile treatment. It is a crucial necessity to determine the mechanisms of PDAC. Y-box Binding Protein 1 (YBX1), a highly conserved transcription factor, has been previously reported to play a role in various hallmarks of cancer. We show here that YBX1 is significantly overexpressed in PDAC and correlates with poor prognosis and reduced survival. In PDAC cell lines, YBX1 regulated cell-cycle progression, proliferation, and the expression of glycogen synthase kinase 3 beta (GSK3B) and cell-cycle-related proteins cyclin D1 and E1. Dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays established that YBX1 binds to the promoter of GSK3B, suggesting that YBX1 promotes pancreatic cancer cell growth through induction of GSK3B expression. These findings offer important insights into the mechanisms underlying pathologic proliferation in PDAC.

| S-EPMC7150436 | biostudies-literature

Long non-coding RNA linc00261 suppresses gastric cancer progression via promoting Slug degradation.

Project description:Gastric cancer (GC) remains a threat to public health with high incidence and mortality worldwide. Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) play critical regulatory roles in cancer biology, including GC. Previous profiling study showed that lncRNA linc00261 was aberrantly expressed in GC. However, the role of linc00261 in GC progression and the precise molecular mechanism remain unknown. In this study, we report that linc00261 was significantly down-regulated in GC tissues and the expression level of linc00261 negatively correlated with advanced tumour status and clinical stage as well as poor prognostic outcome. In vitro functional assays indicate that ectopic expression of linc00261 suppressed cell invasion by inhibiting the epithelial-mesenchymal transition (EMT). By RNA pull-down and mass spectrum experiments, we identified Slug as an RNA-binding protein that binds to linc00261. We confirmed that linc00261 down-regulated Slug by decreasing the stability of Slug proteins and that the tumour-suppressive function of linc00261 can be neutralized by Slug. linc00261 may promote the degradation of Slug via enhancing the interaction between GSK3β and Slug. Moreover, linc00216 overexpression repressed lung metastasis in vivo. Together, our findings suggest that linc00261 acts a tumour suppressor in GC by decreasing the stability of Slug proteins and suppressing EMT. By clarifying the mechanisms underlying GC progression, these findings may facilitate the development of novel therapeutic strategies for GC.

| S-EPMC5387161 | biostudies-literature

The long non-coding RNA AK023948 enhances tumor progression in hepatocellular carcinoma.

Project description:The long non-coding RNAs (lncRNAs) have been demonstrated to play pivotal roles in a broad range of processes including tumor biology. However, the exact contributions of lncRNAs to hepatocellular carcinoma (HCC) remain poorly defined. In current study, we have unraveled a novel function of AK023948 in HCC. We found that AK023948 was substantially upregulated in tumor tissues. Meanwhile, higher AK023948 expression correlated with poor survival. Upregulation of AK023948 expression can promote HepG2 and Hep3B proliferation and invasion in in vitro experiments. Furthermore, AK023948 also decreased tumor growth in vivo. The tumorigenic role of AK023948 was partially ascribed to PI3K/Akt/mTOR signaling and AK023948 knockdown decreased pathway activation and tumor growth. These data collectively suggest an oncogenic role for AK023948 and may provide potential insight into therapeutic intervention.

| S-EPMC5639403 | biostudies-literature

Long non-coding RNA Irm enhances myogenic differentiation by interacting with MEF2D.

Project description:Recent studies suggest important roles for long non-coding RNAs as essential regulators of myogenic differentiation. Here, we report that lncRNA Irm is upregulated during myogenesis. Functional analyses show that the overexpression of Irm enhances myogenic differentiation, whereas the inhibition of Irm has completely opposite effects in vitro. Notably, the inhibition of Irm blocks damage-induced muscle regeneration in vivo. Mechanistically, Irm regulates the expression of myogenic genes by directly binding to MEF2D, which in turn promotes the assembly of MyoD/MEF2D on the regulatory elements of target genes. Collectively, we have identified a novel lncRNA that interacts with MEF2D to regulate myogenesis.

| S-EPMC6385193 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data