Similar Datasets
Project description:Long non-coding RNA H19 promotes the progression of pancreatic cancer by APOBEC3G and both are inhibited by sulforaphane
| PRJNA669753 | ENA
Project description:The vast and promising class of long non-coding RNAs (lncRNAs) has been under investigation for distinct therapeutic applications. Nevertheless, their role as molecular drivers of bone regeneration remains poorly studied. The lncRNA H19 mediates osteogenic differentiation of Mesenchymal Stem/Stromal Cells (MSCs) through the control of intracellular pathways. However, the effect of H19 on the extracellular matrix (ECM) components is still largely unknown. This research study was designed to decode the H19-mediated ECM regulatory network, and to reveal how the decellularized siH19-engineered matrices influence MSC proliferation and fate. This is particularly relevant for diseases in which the ECM regulation and remodelling processes are disrupted, such as osteoporosis.
2023-03-11 | PXD039001 | Pride
Project description:Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant and the therapeutic options available usually have little impact on survival. Great hope is placed on new therapeutic targets, including long noncoding RNAs (lncRNAs), and on the development of new drugs, based on e.g., broccoli-derived sulforaphane, which meanwhile has shown promise in pilot studies in patients. We examined whether sulforaphane interferes with lncRNA signaling and analyzed five PDAC and two nonmalignant cell lines, patient tissues (n = 30), and online patient data (n = 350). RT-qPCR, Western blotting, MTT, colony formation, transwell and wound healing assays; gene array analysis; bioinformatics; in situ hybridization; immunohistochemistry and xenotransplantation were used. Sulforaphane regulated the expression of all of five examined lncRNAs, but basal expression, biological function and inhibition of H19 were of highest significance. H19 siRNA prevented colony formation, migration, invasion and Smad2 phosphorylation. We identified 103 common sulforaphane- and H19-related target genes and focused to the virus-induced tumor promoter APOBEC3G. APOBEC3G siRNA mimicked the previously observed H19 and sulforaphane effects. In vivo, sulforaphane- or H19 or APOBEC3G siRNAs led to significantly smaller tumor xenografts with reduced expression of Ki67, APOBEC3G and phospho-Smad2. Together, we identified APOBEC3G as H19 target, and both are inhibited by sulforaphane in prevention of PDAC progression.
| S-EPMC7920255 | biostudies-literature
Project description:Advanced gallbladder cancer (GBC) is one of the most malignant of all types of biliary tract cancers that is associated with poor prognosis and high mortality. Accumulating evidence suggest that the B7 family of proteins serve an essential role in various types of cancers, including GBC. However, the potential function and regulatory mechanism of human endogenous retrovirus‑H long terminal repeat‑associating protein 2 (HHLA2; also known as B7‑H7 or B7H5) in GBC remain poorly understood. In the present study, immunohistochemistry was used to examine the expression pattern of HHLA2 in samples from 89 patients with GBC. The possible association between HHLA2 expression and the clinicopathological parameters, including prognosis, were then assessed. Using lentiviruses, overexpression of HHLA2 plasmid or short‑hairpin RNA (shRNA) of HHLA2 were transfected into GBC‑SD cells to overexpress or knock down HHLA2 expression, respectively. The effects of HHLA2 overexpression and knockdown on the epithelial‑mesenchymal transition (EMT) process on GBC‑SD cells were measured by the western blotting and immunofluorescence staining of collagen I, N‑cadherin, E‑cadherin, vimentin and α‑SMA. By contrast, changes in cell proliferation were measured using EdU assay. Cell invasion and migration were assessed using Transwell and wound‑healing assays, respectively. In addition, a xenograft mouse model was established to evaluate the tumorigenic ability of the GBC cell line in vivo after stable transfection with lentivirus for HHLA2 overexpression or shRNA for HHLA2 knockdown. The regulatory relationships among TGF‑β1, long non‑coding RNA (lncRNA) H19 (H19) and HHLA2 were then investigated. The mRNA expression of lncRNA H19 were assessed using reverse transcription‑quantitative PCR, whereas the expression levels of HHLA2 were detected by western blotting and immunofluorescence staining. HHLA2 expression was found to gradually increase as the stages of the GBC samples become more advanced. In addition, the expression level of HHLA2 was calculated to be positively associated with the Nevin stage, American Joint Committee on Cancer stage, tumor invasion and regional lymph node metastasis but was negatively associated with the overall patient survival (OS). In vitro experiments demonstrated that overexpression of HHLA2 promoted GBC migration, invasion, proliferation and EMT, whereas in vivo experiments found a promoting role of HHLA2 overexpression on GBC tumor growth. After transfection with lentiviruses encoding the overexpression plasmid of lncRNA H19, GBC migration, invasion, proliferation and EMT were increased. By contrast, knocking down HHLA2 expression suppressed TGF‑β1‑ or lncRNA H19 overexpression‑induced GBC migration, invasion, proliferation and EMT. In addition, HHLA2 knockdown significantly reduced the sizes of the GBC tumors in vivo. These results suggest that HHLA2 overexpression can promote GBC progression. Conversely, ablation of HHLA2 expression inhibited both TGF‑β1‑ and lncRNA H19‑induced GBC progression, suggesting that HHLA2 is a potential therapeutic target for this disease.
| S-EPMC9374468 | biostudies-literature
Project description:Long non-coding RNA H19
2021-12-31 | GSE175865 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality, which threats peoples' health. Unfortunately, the pathogenesis of PDAC remains unclear. Recent studies have indicated that long non-coding RNAs (lncRNAs) can regulate the development and progression of malignant tumors through varying mechanisms. LncRNA H19 has a unique expression profile and can act as a sponger of specific miRNAs to regulate the pathogenic process of many diseases, including PDAC and several other types of cancers. Here, we review the research approaches to understanding the regulatory role of H19 and potential mechanisms in the progression of PDAC and other types of cancers and diseases. These studies suggest that H19 may be a novel therapeutic target for PDAC and our findings may open new revenues for scientific researches and development of valuable therapies for these diseases in the future.
| S-EPMC7146949 | biostudies-literature
Project description:We used high throughput sequencing to compare the differential gene expression of HepG2 cells with and without H19 knockdown. We found critical genes involved in glucose production changed significantly after H19 konckdown compared to control.
2018-08-30 | GSE103201 | GEO
Project description:To determine the functional epigenetic landscape of changes induced by H19, ChIP-seq was performed on H3K27me3 and H3K4me3 in V16D CRPC cells transduced with H19 (to induce NEtD) versus V16D CRPC control cells. Comaparison of genome-wide maps of chromatin state in V16D CRPC cells with and without H19 overexpression.
2021-09-15 | GSE183983 | GEO
Project description:Soleus muscle has the most abundant H19 expression compared to other skeletal muscle tissues. In order to identify genes regulated by long noncoding RNA H19 in skeletal muscle, we performed RNA-Seq with dissected WT and H19KO soleus muscles from 21 week old mice. Among the differentially expressed genes, we found skeletal muscle - overexpressed gene DUSP27, which potentially plays an important role in regulating skeletal muscle glucose metabolisim by regulating the activitiy of AMPK, might be a target of H19 mediated regulation.
2018-08-30 | GSE103202 | GEO
Project description:Imprinted genes occur in discrete clusters that are coordinately regulated by shared DNA elements. H19 and Igf2 are linked imprinted genes that play critical roles in development. Loss of imprinting at the IGF2/H19 locus is associated with Beckwith Wiedemann Syndrome (BWS). Here we use comprehensive genetic and genomic analyses to follow muscle development in a mouse model of BWS to dissect the separate and shared roles for Igf2 and H19 in the disease phenotype. We show that LOI results in defects in muscle differentiation and hypertrophy and we identify primary downstream targets of Igf2 (MAPK signaling) and of H19 (AKT/mTOR signaling). Moreover, we demonstrate instances where H19 and Igf2 misexpression work separately, cooperatively, and also antagonistically to establish the disease phenotype. This study underscores the fact that LOI phenotypes are multigenic and complex interactions contribute to disease outcomes.
2017-09-25 | GSE89136 | GEO