LncRNA SPRY4-IT1 Facilitates Cell Proliferation and Angiogenesis of Glioma by the miR-101-3p/EZH2/VEGFA Signaling Axis
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ABSTRACT:
PROVIDER: PRJNA783050 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17022358_1.fastq.gz | Fastqsanger.gz | |||
| SRR17022358_2.fastq.gz | Fastqsanger.gz | |||
| SRR17022359_1.fastq.gz | Fastqsanger.gz | |||
| SRR17022359_2.fastq.gz | Fastqsanger.gz | |||
| SRR17022361_1.fastq.gz | Fastqsanger.gz |
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Project description:SPRY4-IT1 (SPRY4 intronic transcript 1) is a long non-coding RNA (lncRNA) that was identified as a novel oncogene in various human cancers, including glioma. However, its function and the further mechanism in glioma remain largely unclear. Here, we aimed to investigate the role of SPRY4-IT1 in the development of glioma and its underlying molecular mechanism. We identify that SPRY4-IT1 is overexpressed in patients with glioma from the TCGA database and own cohort, and correlated with poor prognosis of patients. Then, loss of function and gain of function cell model were established by transfected with siRNA and pcDNA3.1 plasmid. SPRY4-IT1 promotes glioma cells proliferation by Cell Count Kit 8 assays and EdU assay in vitro, and xenograft tumor assays in vivo. RNA sequence was performed to compare the transcriptomes of U87 siSPRY4-IT1-NC and U87 siSPRY4-IT1 cells, and Gene Ontology (GO) enrichment analysis indicated angiogenesis is significantly enriched. HUVEC tube forming assays and Chick Embryo Chorioallantoic Membrane (CAM) assays confirmed that SPRY4-IT1 can induce angiogenesis of glioma in vitro and in vivo. Mechanistically, we identify that SPRY4-IT1 upregulates EZH2 expression by sponge miR-101-3p to induce VEGFA expression in glioma cells. Moreover, SPRY4-IT1 activates VEGFR2/AKT/ERK1/2 pathway in HUVECs by glioma cell-mediated. Rescue experiments were performed by co-transfected with SPRY4-IT1 and EZH2 overexpression plasmid in glioma cells, and confirmed that SPRY4-IT1 promotes cell proliferation and angiogenesis of glioma by miR-101-3p/EZH2/VEGFA signaling axis. Taken together, our studies clarify that SPRY4-IT1 upregulates EZH2 to induce VEGFA by sponge miR-101-3p to achieve cell proliferation and angiogenesis in glioma. Thus, these findings have provided insights into the prognosis prediction and therapeutic target of glioma.
2022-06-30 | GSE189462 | GEO
Project description:The bivalent domain at promoter region is a unique epigenetic feature poised for activation or repression during cell differentiation in embryonic stem cell. However, the function of bivalent domains in already differentiated cells remains exclusive. By profiling the epigenetic landscape of endothelial cells during VEGFA stimulation, we discovered that bivalent domains are widespread in endothelial cells and preferentially marked genes responsive to VEGFA. The bivalent domains responsive to VEGFA have more permissive chromatin environment comparing to other bivalent domains. The initial activation of bivalent genes depends on RNAPII pausing release induced by EZH1 rather than removal of H3K27me3. The later suppression of bivalent gene expression depended on KDM5A recruitment by its interaction with PRC2. Importantly, EZH1 promoted both in vitro and in vivo angiogenesis by upregulating EGR3, whereas KDM5A dampened angiogenesis. Collectively, this study demonstrated a novel dual function of bivalent domains in endothelial cells to control VEGF responsiveness and angiogenesis.
2020-10-17 | GSE139077 | GEO
Project description:Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis
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Project description:Background: Long noncoding RNAs (lncRNAs) have emerged recently as a new class of genes regulating cellular processes, such as cell growth and apoptosis. The SPRY4 intronic transcript 1 (SPRY4-IT1) is a 708-bp lncRNA on chromosome 5 with a potential functional role in tumorigenesis. The clinical significance of SPRY4-IT1 and the effect of SPRY4-IT1 on cancer progression are unclear. Methods: Quantitative reverse transcriptase PCR (qRT-PCR) was performed to investigate the expression of SPRY4-IT1 in 48 breast cancer tissues and four breast cancer cell lines. Gain and loss of function approaches were used to investigate the biological role of SPRY4-IT1 in vitro. Microarray bioinformatics analysis was performed to identify the putative targets of SPRY4-IT1, which were further verified by rescue experiments, as well as by western blotting and qRT-PCR. Results: SPRY4-IT1 expression was significantly upregulated in 48 breast cancer tumor tissues compared to normal tissues. Additionally, increased SPRY4-IT1 expression was associated with larger tumor size and an advanced pathological stage in breast cancer patients. Knockdown of SPRY4-IT1 significantly suppressed proliferation and caused apoptosis of breast cancer cells in vitro. Furthermore, we discovered ZNF703 was a direct target of SPRY4-IT1 and was downregulated by SPRY4-IT1 knockdown. Moreover, we demonstrated for the first time that ZNF703 is a genetic driver in ER (-) breast carcinoma cells. Conclusions: SPRY4-IT1 is a novel prognostic biomarker and a potential therapeutic candidate for breast cancer. Five samples are analyzed, including three control groups and two small interfering RNA groups
2014-10-22 | E-GEOD-62507 | biostudies-arrayexpress
Project description:The functional analysis of RUNX1-IT1 in tumors is relatively lacking, and its role and mechanism in pancreatic have not been reported. RUNX1-IT1 is transcribed from the intron of the RUNX1 gene, which plays an important role in solid tumors, and its abnormal expression is closely associated with cancer progression. However, due to the lack of systematic research, the regulatory mechanism and important downstream targets of RUNX1-IT1 and RUNX1 in PC are unclear. To investigate the downstream pathway of RUNX1-IT1 and RUNX1, we performed RNA-seq using two PANC-1 cell groups: RUNX1-IT1 knockdown and control, and RUNX1 knockdown and control.
2022-08-13 | GSE135783 | GEO
Project description:To investigate the function of RUNX1-IT1 in ovarian cancer progression, we constructed ES2 cell lines with knockdown of RUNX1-IT1 and the control group. We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 different cells.
2024-01-01 | GSE245778 | GEO
Project description:Background: Long noncoding RNAs (lncRNAs) have emerged recently as a new class of genes regulating cellular processes, such as cell growth and apoptosis. The SPRY4 intronic transcript 1 (SPRY4-IT1) is a 708-bp lncRNA on chromosome 5 with a potential functional role in tumorigenesis. The clinical significance of SPRY4-IT1 and the effect of SPRY4-IT1 on cancer progression are unclear. Methods: Quantitative reverse transcriptase PCR (qRT-PCR) was performed to investigate the expression of SPRY4-IT1 in 48 breast cancer tissues and four breast cancer cell lines. Gain and loss of function approaches were used to investigate the biological role of SPRY4-IT1 in vitro. Microarray bioinformatics analysis was performed to identify the putative targets of SPRY4-IT1, which were further verified by rescue experiments, as well as by western blotting and qRT-PCR. Results: SPRY4-IT1 expression was significantly upregulated in 48 breast cancer tumor tissues compared to normal tissues. Additionally, increased SPRY4-IT1 expression was associated with larger tumor size and an advanced pathological stage in breast cancer patients. Knockdown of SPRY4-IT1 significantly suppressed proliferation and caused apoptosis of breast cancer cells in vitro. Furthermore, we discovered ZNF703 was a direct target of SPRY4-IT1 and was downregulated by SPRY4-IT1 knockdown. Moreover, we demonstrated for the first time that ZNF703 is a genetic driver in ER (-) breast carcinoma cells. Conclusions: SPRY4-IT1 is a novel prognostic biomarker and a potential therapeutic candidate for breast cancer.
2014-10-22 | GSE62507 | GEO
Project description:VEGFA signaling is crucial for physiological and pathological angiogenesis and hematopoiesis. Although many context-dependent signaling pathways downstream of VegfA have been uncovered, vegfa transcriptional regulation in vivo is unclear. Here, we show that ETS transcription factor Etv6 positively regulates vegfa expression during blood stem cell development through multiple transcriptional inputs. In agreement with its established repressive functions, Etv6 directly inhibits expression of vegfa repressor foxo3. Surprisingly, it also directly activates expression of vegfa activator klf4. Finally, it indirectly binds to vegfa promoter by the recruiment of Klf4. Thus, our work uncovers a dual function for Etv6, as both a transcriptional repressor and activator, in controlling a major signaling pathway.
2019-01-16 | GSE115224 | GEO
Project description:VEGFA signaling is crucial for physiological and pathological angiogenesis and hematopoiesis. Although many context-dependent signaling pathways downstream of VegfA have been uncovered, vegfa transcriptional regulation in vivo is unclear. Here, we show that ETS transcription factor Etv6 positively regulates vegfa expression during blood stem cell development through multiple transcriptional inputs. In agreement with its established repressive functions, Etv6 directly inhibits expression of vegfa repressor foxo3. Surprisingly, it also directly activates expression of vegfa activator klf4. Finally, it indirectly binds to vegfa promoter by the recruiment of Klf4. Thus, our work uncovers a dual function for Etv6, as both a transcriptional repressor and activator, in controlling a major signaling pathway.
2019-01-16 | GSE115220 | GEO
Project description:LncRNA ENO1-IT1 has been found to be mainly located in the nucleus of colorectal mucosa epithelial cells, which indicates that this lncRNA may be responsible for regulating the expression of target gene. To address whether ENO1-IT1 modulates epigenetic changes genome-wide, we performed chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) in HCT116 cells
2022-10-25 | GSE139403 | GEO