Similar Datasets
Project description:We shed light on a closely cooperative machinery between HSF1 and super enhancer for the first time in CRC. HSF1 could stimulate super enhancer activity by the enrichment of acetyltransferase P300 to LINC00857 promoter region, contributing to LINC00857 transcription.
2022-08-15 | GSE198224 | GEO
Project description:We shed light on a closely cooperative machinery between HSF1 and super enhancer for the first time in CRC. HSF1 could stimulate super enhancer activity by the enrichment of acetyltransferase P300 to LINC00857 promoter region, contributing to LINC00857 transcription.
2022-08-15 | GSE198223 | GEO
Project description:Super enhancers are critical for the gene transcription responsible for cell fate by interacting with transcription factors. However, the relevance of HSF1 to super enhancers in tumors remains obscure. We profiled H3K27ac enrichment by chromatin immunoprecipitation sequencing. HSF1-mediated lncRNAs were identified by lncRNA microarray. The characteristics of LINC00857 were explored by in vitro and in vivo assays. The mechanism was studied via chromatin immunoprecipitation, RNA immunoprecipitation, and HSF1/ANXA11 knockout mice. We found that super enhancers occupied multiple gene loci in colorectal cancer. We screened out an HSF1-mediated super enhancer, lncRNA-LINC00857, which exerts its characteristics in promoting cell growth via regulating glutamine metabolism. Notably, HSF1 could stimulate the super-enhancer activity of LINC00857 by the enrichment of acetyltransferase P300 to its gene loci, contributing to LINC00857 transcription. In turn, nuclear LINC00857 cooperated with HSF1 to promote ANXA11 transcription, which modulated SLC1A5/ASCT2 protein expression by binding competitively to miR-122-5p. The knockout of ANXA11 attenuated colorectal cancer formation in vivo. Collectively, we shed light on a closely cooperative machinery between HSF1 and super enhancers. HSF1 could stimulate acetyltransferase P300-mediated super-enhancer activity to facilitate LINC00857 expression, contributing to SLC1A5-mediated glutamine transport. Targeting the HSF1/LINC00857/ANXA11 axis may provide a valuable therapeutic strategy against colorectal cancer.
| S-EPMC9406190 | biostudies-literature
Project description:HSF1 activates ANXA11-mediated glutamine metabolism by super enhancer long non-coding RNA LINC00857 in colorectal cancer.
| PRJNA814242 | ENA
Project description:HSF1 activates ANXA11-mediated glutamine metabolism by super enhancer long non-coding RNA LINC00857 in colorectal cancer [array]
| PRJNA814243 | ENA
Project description:HSF1 activates ANXA11-mediated glutamine metabolism by super enhancer long non-coding RNA LINC00857 in colorectal cancer [ChIP-seq]
| PRJNA814244 | ENA
Project description:We have ablated the cellular RNA degradation machinery in differentiated B cells and pluripotent embryonic stem cells (ESCs) by conditional mutagenesis of core (Exosc3) and nuclear RNase (Exosc10) components of RNA exosome and identified a vast number of long non-coding RNAs (lncRNAs) and enhancer RNAs (eRNAs) with emergent functionality. Unexpectedly, eRNA-expressing regions accumulate R-loop structures upon RNA exosome ablation, thus demonstrating the role of RNA exosome in resolving deleterious DNA/RNA hybrids arising from active enhancers. We have uncovered a distal divergent eRNA-expressing element (lncRNA-CSR) engaged in long-range DNA interactions and regulating IgH 3' regulatory region super-enhancer function. CRISPR-Cas9-mediated ablation of lncRNA-CSR transcription decreases its chromosomal looping-mediated association with the IgH 3' regulatory region super-enhancer and leads to decreased class switch recombination efficiency. We propose that the RNA exosome protects divergently transcribed lncRNA expressing enhancers by resolving deleterious transcription-coupled secondary DNA structures, while also regulating long-range super-enhancer chromosomal interactions important for cellular function.
| S-EPMC4428671 | biostudies-literature
Project description:Super-enhancer-associated long non-coding RNAs (SE-lncRNAs) are a specific set of lncRNAs transcribed from super-enhancer (SE) genomic regions. Recent studies have revealed that SE-lncRNAs play essential roles in tumorigenesis through the regulation of oncogenes. The objective of this study was to elucidate the expression profile of SE-lncRNAs with concurrent assessment of associated mRNAs in leiomyomas and paired myometrium. Arraystar SE-lncRNAs arrays were used to systematically profile the differentially expressed SE-lncRNAs along with the corresponding SE-regulated protein coding genes in eight leiomyomas and paired myometrium. The analysis indicated 7680 SE-lncRNAs were expressed, of which 721 SE-lncRNAs were overexpressed, while 247 SE-lncRNAs were underexpressed by 1.5-fold or greater in leiomyoma. Thirteen novel SE-lncRNAs and their corresponding protein coding genes were selected, and their expression was confirmed in eighty-one paired leiomyoma tissues by quantitative real-time PCR. The thirteen pairs of SE-lncRNAs and their corresponding protein coding genes included RP11-353N14.2/CBX4, SOCS2-AS1/SOCS2, RP1-170O19.14/HOXA11, CASC15/PRL, EGFLAM-AS1/EGFLAM, RP11-225H22/NEURL1, RP5-1086K13.1/CD58, AC092839.3/SPTBN1, RP11-69I8.3/CTGF, TM4SF1-AS1/TM4SF1, RP11-373D23/FOSL2, RP11-399K21.11/COMTD1, and CTB-113P19.1/SPARC. Among these SE-lncRNAs, the expression of SOCS2-AS1/SOCS2, RP11-353N14.2/CBX4, RP1-170O19.14/HOXA11, and RP11-225H22/NEURL1 was significantly higher in African Americans as compared with Caucasians. The expression of RP11-353N14.2/CBX4, SOCS2-AS1/SOCS2, CASC15/PRL, and CTB-113P19.1/SPARC was significantly higher in tumors with MED12-mutation-positive as compared with MED12-mutation-negative tumors. Collectively, our results indicate that the differential expression of SE in leiomyomas is another mechanism contributing to dysregulation of protein coding genes in leiomyomas and that race and MED12 mutation can influence the expression of a select group of SE.
| S-EPMC9537225 | biostudies-literature
Project description:Here, we investigated the clinicopathological and prognostic potential of the long noncoding RNA Colon Cancer-Associated Transcript 2 (CCAT2) in human colorectal cancer (CRC). We used qPCR to quantify CCAT2 levels in 44 pairs of CRC tissues and adjacent nontumor and healthy colon mucosa tissues, and in several CRC cell lines (SW620, SW480, HT-29, LOVO, HCT116 and DLD-1) and normal human colorectal epithelial cells (HFC). We assessed the effects of CCAT2 overexpression or knockdown on the proliferation, migration and invasion by SW620 and LOVO cells using CCK-8, transwell, and wound-healing assays, respectively. We also investigated the potential interaction between CCAT2 and TAF15 through RNA pull down and rescue experiments. Lastly, we evaluated the expression of the cell cycle progression markers and GSK3β signaling pathway proteins using Western blotting. Our results showed that CCAT2 was upregulated in CRC tissues and cell lines as com-pared to controls. Ectopic expression of CCAT2 promoted CRC cell proliferation, migration and invasion, likely through direct interaction with TAF15, transcriptional activation of RAB14, and activation of the AKT/GSK3β signaling pathway. In vivo, CCAT2 promoted CRC cell growth and metastasis in nude mice. Taken together, these results highlight the actions of CCAT2 as a CRC oncogene.
| S-EPMC8639683 | biostudies-literature
Project description:BackgroundGlutamine (Gln) metabolism has been confirmed as an important fuel in cancer metabolism. This study aimed to uncover potential links of Gln with long non-coding RNAs (lncRNAs) and the prognostic value of Gln-associated lncRNAs in multiple myeloma (MM) patients.MethodsThe RNA-seq expression profile and corresponding clinical data of gastric cancer obtained from Gene Expression Omnibus (GEO) database. Unsupervised consensus clustering was used to cluster MM samples based on Gln-associated lncRNAs. The overall survival (OS), biological pathways, and immune microenvironment were compared in different subtypes. Differential analysis was utilized to identify differentially expressed lncRNAs (DElncRNAs) in different subtypes. A risk model was constructed based on DElncRNAs by using Cox regression, least absolute shrinkage and selection operator (LASSO), and the stepAIC algorithm.ResultsWe screened 50 Gln-associated lncRNAs and identified 3 molecular subtypes (clust1, clust2, and clust3) based on lncRNA expression profiles. Clust3 subtype showed the worst prognosis and highest enrichment of Gln metabolism pathway. Angiogenesis, epithelial-mesenchymal transition (EMT), and cell cycle-related pathways were relatively activated in clust3. Then, we identified 11 prognostic DElncRNAs for constructing the risk model. The MM samples were divided into high- and low-risk groups with distinct prognosis according to the risk score. The risk score was significantly associated with cell cycle and infiltration of many immune cells.ConclusionsThis study characterized the role of Gln-associated lncRNAs in Gln metabolism contributing for tumor-related pathways and immune microenvironment in MM patients. The 11 lncRNAs in the risk model may serve as potential targets for exploring the mechanism of Gln metabolism or serve as potential biomarkers for MM prognosis.
| S-EPMC9843343 | biostudies-literature