Long non-coding RNA RP11-19E11.1 is an E2F1 target required for tumor cell proliferation and survival in basal breast cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA576500 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10247645.fastq.gz | Fastqsanger.gz | |||
| SRR10247646.fastq.gz | Fastqsanger.gz | |||
| SRR10247647.fastq.gz | Fastqsanger.gz | |||
| SRR10247648.fastq.gz | Fastqsanger.gz | |||
| SRR10247649.fastq.gz | Fastqsanger.gz |
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Project description:Long non-coding RNAs (lncRNAs) play key roles in the regulation of breast cancer initiation and progression. LncRNAs are differentially expressed in breast cancer subtypes. Basal-like breast cancers are generally poorly differentiated tumors, are enriched in embryonic stem cell signatures, lack expression of estrogen receptor, progesterone receptor, and HER2 (triple negative breast cancer, TNBC), and show activation of proliferation-associated factors. We hypothesized that lncRNAs are key regulators of basal breast cancers. Using The Cancer Genome Atlas we identified lncRNAs that are overexpressed in basal tumors compared to other breast cancer subtypes and expressed in at least 10% of patients. Remarkably, we identified lncRNAs whose expression correlated with patient prognosis. We then evaluated the function of a subset of lncRNA candidates in the oncogenic process in vitro. Here, we report the identification and characterization of the chromatin-associated lncRNA, RP11-19E11.1, which is up-regulated in 40% of basal primary breast cancers. Gene set enrichment analysis in primary tumors and in cell lines uncovered a correlation between RP11-19E11.1 expression level and the E2F oncogenic pathway. We show that this lncRNA is chromatin-associated and an E2F1 target, and its expression is necessary for cancer cell proliferation and survival. Finally, we used lncRNA expression levels as a tool for drug discovery in vitro, identifying Protein Kinase C (PKC) as a potential therapeutic target for a subset of basal-like breast cancers. Our findings suggest lncRNA overexpression is clinically relevant. Understanding deregulated lncRNA expression in basal-like breast cancer may lead to potential prognostic and therapeutic applications.
2019-12-11 | GSE138606 | GEO
Project description:Long non-coding RNAs (lncRNAs) play key roles in the regulation of breast cancer initiation and progression. LncRNAs are differentially expressed in breast cancer subtypes. Basal-like breast cancers are generally poorly differentiated tumors, are enriched in embryonic stem cell signatures, lack expression of estrogen receptor, progesterone receptor, and HER2 (triple-negative breast cancer), and show activation of proliferation-associated factors. We hypothesized that lncRNAs are key regulators of basal breast cancers. Using The Cancer Genome Atlas, we identified lncRNAs that are overexpressed in basal tumors compared to other breast cancer subtypes and expressed in at least 10% of patients. Remarkably, we identified lncRNAs whose expression correlated with patient prognosis. We then evaluated the function of a subset of lncRNA candidates in the oncogenic process in vitro. Here, we report the identification and characterization of the chromatin-associated lncRNA, RP11-19E11.1, which is upregulated in 40% of basal primary breast cancers. Gene set enrichment analysis in primary tumors and in cell lines uncovered a correlation between RP11-19E11.1 expression level and the E2F oncogenic pathway. We show that this lncRNA is chromatin-associated and an E2F1 target, and its expression is necessary for cancer cell proliferation and survival. Finally, we used lncRNA expression levels as a tool for drug discovery in vitro, identifying protein kinase C (PKC) as a potential therapeutic target for a subset of basal-like breast cancers. Our findings suggest that lncRNA overexpression is clinically relevant. Understanding deregulated lncRNA expression in basal-like breast cancer may lead to potential prognostic and therapeutic applications.
| S-EPMC6944689 | biostudies-literature
Project description:Downregulations of TCAM1P-004 and RP11-598D14.1 were frequently observed in HCC tumors as compared to adjacent non-tumor tissues. To further study the molecular functions of TCAM1P-004 and RP11-598D14.1, we attempted to identify the gene targets regulated by either lncRNAs. Knockdown of TCAM1P-004 or RP11-598D14.1 were achieved by transduction of lentivirus carrying respective shRNAs in non-tumor hepatocyte MIHA cells. Diffferentially expressed genes after knockdown of the lncRNAs were compared to cells tranduced with lentivirus carrying scramble shRNAs.
2018-10-24 | E-MTAB-7280 | biostudies-arrayexpress
Project description:Objective: The aim of this study was to reveal the function of the long non-coding RNA (lncRNA) RP11-556E13.1 (RP11) and its clinical significance in hepatocellular carcinoma. Methods: LncRNA and mRNA expression profiling was performed using lncRNA and mRNA microarrays in 5 pairs of HCC and adjacent tissues. 112 paired HCC and adjacent tissue samples were analyzed by semiquantitative real-time polymerase chain reaction (sqRT-PCR) to evaluate the expression of RP11 and its possible associated clinical significance. Smart silencer RNA (siRNA) was used to knockdown the expression of RP11 in HCC cells. After knockdown, the function of RP11 was determined in vitro using some kinds of cell functional experiments in HCC cells including cell proliferation assay, cell apoptosis assay and cell cycle assay. Western blotting (WB) was performed to detect proteins that were presumably associated with these functional changes. An Affymetrix Human HTA2.0 microarray was used to detect differentially expressed genes in HCC cells after RP11 knockdown. GO enrichment and KEGG pathway enrichment analysis were then performed to elucidate the biological roles of these differentially expressed mRNAs.
2022-04-18 | GSE200861 | GEO
Project description:Transfection experiments aimed at understanding the impact of upregulation a lncRNA (RP11-326A19.4) on genome-wide transcription
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Project description:To further explore t of the role lncRNAs in glaucoma patients, we have employed lncRNAs microarray expression profiling as a discovery platform to identify abnormal genes under oxidative stress in HTMCs. Our results revealed that lncRNA-RP11 was significantly up-regulated under oxidative stress in HTMCs. Further studies found that lncRNA-RP11-820 directly binds miR-3178, through which regulates the expression of MYOD1. Importantly, MYOD1 can transcriptionally activate ECM genes. Furthermore, MYOD1 binds STAT3 to form a transcription complex, and transcriptionally activates ECM genes expression in HTMCs. Taken together, our data established taht oxidative stress induced lncRNA-RP11-820 plays a key role in regulating miR-3178/MYOD1/ECM axis in HTMCs.
2019-02-07 | GSE126170 | GEO
Project description:The long non-coding RNA SLNCR and the transcription factor E2F1 both have oncogenic activities in melanoma. Here we show that melanoma metastasis depends upon the formation of an oncogenic SLNCR–E2F1 complex. Unbiased computational analyses of patient samples revealed worse overall survival only in melanoma patients overexpressing both SLNCR and E2F1. Blocking SLNCR–E2F1 complex formation without reducing the levels of either SLNCR or E2F1 reversed melanoma invasion ex vivo and melanoma extravasation in mice. We discovered that E2F1 bound to sequences in SLNCR that are the RNA analogs of the E2F consensus DNA-binding element, suggesting that RNA and DNA binding engages the same domain in E2F1. Binding competition assays demonstrated that E2F1 preferentially bound to RNA compared to its cognate DNA element and that RNA efficiently competed with the consensus DNA-binding element for E2F1 binding. Molecular dynamics simulations indicated increased thermodynamic stability of E2F1–DNA interactions as compared to E2F1–RNA interactions. However, molecular dynamics simulations also indicated greater number of RNA-amino acid contacts within the E2F1 DNA binding domain (E2F1DBD) than DNA. This suggests better kinetic binding properties of RNA to the E2F1DBD as compared to DNA and may explain how RNA efficiently competed with DNA for E2F1DBD binding. E2F1 often binds to DNA as a heterodimer with DP1. Molecular dynamics simulations suggested that RNA binding to E2F1 may prevent E2F1–DP1 heterodimerization by masking key amino acids required for DP1 binding. These data reveal the SLNCR-driven oncogenic activities of E2F1 and identify the SLNCR–E2F1 complex as a target for future melanoma therapy.
2025-06-17 | GSE270372 | GEO
Project description:dCas9 activation of RP11-326A19.4
| PRJNA548121 | ENA
Project description:Through deep RNA-seq of human monocyte-derived macrophages, we identified RP11-184M15.1, a human macrophage-specific lincRNA, to be highly induced in the cytoplasm of IL-4-stimulated macrophage. Preliminary data showed that treatment of IL-4-stimulated THP1 human macrophages with RP11-184M15.1 small interfering RNA (siRNA) repressed apoptosis of resolving macrophages, as shown by decreased Annexin V+ macrophages, and reduced protein expression of cleaved PARP. Biotinylated RP11-184M15.1 pulldown coupled with mass spectrometry indicated an interaction between RP11-184M15.1 and zinc finger RNA-binding protein (ZFR). RIP corroborated the proposed interaction between RP11-184M15.1 and ZFR. RNAInter revealed mRNAs predicted to interact with ZFR, and some of those genes (e.g., ALYREF, CCNYL1) were also differentially expressed in RNA-seq data of control versus RP11-184M15.1 knockdown in IL-4-stimulated THP1 macrophages. qPCR validated that ALYREF and CCNYL1 expression are reduced with RP11-184M15.1 knockdown. In contrast, with ZFR siRNA, ALYREF and CCNYL1 mRNA expressions were elevated. Thus, a hypothesis to be further tested is that RP11-184M15.1 interacts with ZFR to regulate mRNA stability in IL-4-stimulated macrophages. Nuclear RNA export factor 1 (NXF1) was also validated by RIP to interact with RP11-184M15.1. NXF1 is a known interacting partner of ALYREF in the transcription-export (TREX) complex. With RP11-184M15.1 knockdown, the protein level of ALYREF decreased, and Ingenuity Pathway Analysis (IPA) of RNA-seq data of control versus RP11-184M15.1 knockdown revealed that THO complex subunit 5 homolog (THOC5), another component of the TREX complex, may be an upstream regulator. In addition, past studies have revealed that ALYREF and NXF1 are involved in nuclear export of inflammatory mRNAs and proinflammatory macrophage phenotype, respectively. With RP11-184M15.1 knockdown, there was decreased expression of inflammatory macrophage-associated genes. It may be possible that RP11-184M15.1 functions in mRNA export, along with NXF1 and ALYREF.
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Project description:Transfection experiments aimed at understanding the impact of upregulating lncRNA RP11-326A19.4 on the transcriptome; follow-up of GSE132451
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