The lncRNA RUNX1-IT1 promotes pancreatic cancer progression by inducing C-FOS expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE135783 | GEO | 2022/08/13
REPOSITORIES: GEO
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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. Five samples are analyzed, including three control groups and two small interfering RNA groups
2014-10-22 | E-GEOD-62507 | biostudies-arrayexpress
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:Numerous long noncoding RNAs (lncRNAs) are aberrantly expressed in pancreatic cancer (PC); however, their functions and mechanisms in cancer progression are largely unknown. In this study, we identified a novel PC-associated lncRNA, RUNX1-IT1, that was significantly upregulated in PC patient samples from multiple centers and associated with poor prognosis. In vitro and in vivo, alterations in RUNX1-IT1 expression markedly affected PC proliferation, migration and invasion. RUNX1-IT1 contributed to the progression of PC by interacting with the adjacent gene RUNX1. Rescue experiments showed that RUNX1 reduced the cancer-promoting effect of RUNX1-IT1. RNA-seq analysis after silencing RUNX1-IT1 and RUNX1 highlighted alterations in the common target C-FOS. Mechanistically, we demonstrated that RUNX1-IT1 was a trans-acting factor that participated in the proliferation, migration and invasion of PC by recruiting RUNX1 to the C-FOS gene promoter. Furthermore, RUNX1-IT1 enhanced the transcription of the RUNX1 gene, indicating its potential as a cis-regulatory RNA involved in the upstream regulation of RUNX1. Overall, RUNX1-IT1 is a crucial oncogenic lncRNA that activates C-FOS expression by regulating and recruiting RUNX1 and is a potential prognostic biomarker and therapeutic target for PC.
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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.
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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
Project description:The transcription factor RUNX1 exhibits recurrent loss-of-function mutations in estrogen receptor-positive (ER+) breast cancer (BCa). Its knockdown in vitro decreased AXIN1 expression in estrogen-dependent manner. Consistently, RUNX1 and AXIN1 mRNA levels are strongly correlated in ER+, not ER- tumors. RUNX1 occupies AXIN1â??s second intron in living cells, abutting an ERa-binding site. Potentially promoting BCa progression, decreased AXIN1 expression after RUNX1 knockdown associated with upregulation of b-catenin, and this was preventable by AXIN stabilizers. Unlike in colon cancer, however, deregulation of b-catenin in BCa cells affect neither c-Myc, nor CCND1, nor G1/S cell cycle phase transition. Instead, cyclin B1 was decreased and the G2/M checkpoint was compromised as indicated by mitotic slippage in the presence of microtubule disruptors. Thus, combined analysis of the RUNX1 transcriptome, its cistrome, and differential mRNA expression in tumors with wild type versus mutant RUNX1, altogether highlight a role for the RUNX1/AXIN1/b-catenin axis in ER+ BCa. Significance: Three recent exome sequencing studies assigned to RUNX1 a BCa suppressor role. The present study begins to uncover the underlying molecular mechanisms, offers an explanation for the specificity to ER+ tumors, and marks AXIN1 as a therapeutic target for ER+/RUNX1- BCa. Examination of RUNX1 binding in MCF7 cells
2016-02-22 | E-GEOD-65313 | biostudies-arrayexpress
Project description:The transcription factor RUNX1 exhibits recurrent loss-of-function mutations in estrogen receptor-positive (ER+) breast cancer (BCa). Its knockdown in vitro decreased AXIN1 expression in estrogen-dependent manner. Consistently, RUNX1 and AXIN1 mRNA levels are strongly correlated in ER+, not ER- tumors. RUNX1 occupies AXIN1’s second intron in living cells, abutting an ERa-binding site. Potentially promoting BCa progression, decreased AXIN1 expression after RUNX1 knockdown associated with upregulation of b-catenin, and this was preventable by AXIN stabilizers. Unlike in colon cancer, however, deregulation of b-catenin in BCa cells affect neither c-Myc, nor CCND1, nor G1/S cell cycle phase transition. Instead, cyclin B1 was decreased and the G2/M checkpoint was compromised as indicated by mitotic slippage in the presence of microtubule disruptors. Thus, combined analysis of the RUNX1 transcriptome, its cistrome, and differential mRNA expression in tumors with wild type versus mutant RUNX1, altogether highlight a role for the RUNX1/AXIN1/b-catenin axis in ER+ BCa. Significance: Three recent exome sequencing studies assigned to RUNX1 a BCa suppressor role. The present study begins to uncover the underlying molecular mechanisms, offers an explanation for the specificity to ER+ tumors, and marks AXIN1 as a therapeutic target for ER+/RUNX1- BCa.
2016-02-22 | GSE65313 | GEO
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Project description:Despite absent expression in normal hematopoiesis, the Forkhead factor FOXC1, a critical mesenchymal differentiation regulator, is highly expressed in ~30% of HOXAhigh AML to confer blocked monocyte/macrophage differentiation. Through integrated proteomics and bioinformatics, we discovered that FOXC1 and RUNX1 interact through Forkhead and Runt domains respectively and cooccupy primed and active enhancers distributed close to differentiation genes. FOXC1 stabilises association of RUNX1, HDAC1 and Groucho repressor TLE3 to limit enhancer activity: FOXC1 knockdown induced loss of repressor proteins, gain of CEBPA binding, enhancer acetylation and upregulation of nearby genes, including KLF2. Furthermore, it triggered genome-wide redistribution of RUNX1, TLE3 and HDAC1 from enhancers to promoters leading to repression of self-renewal genes including MYC and MYB. Our studies highlight RUNX1 and CEBPA transcription factor swapping as a feature of leukemia cell differentiation, and reveal that FOXC1 prevents this by stabilising enhancer binding of a RUNX1/HDAC1/TLE3 transcription repressor complex, to oncogenic effect.
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