MiRNA expression data before and after TGF-β treatment and Ago2-associated transcripts in lung fibroblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE86186 | GEO | 2017/11/01
SECONDARY ACCESSION(S): PRJNA340482
REPOSITORIES: GEO
Similar Datasets
Project description:miRNA expression data before and after TGF-β treatment and Ago2-associated transcripts in lung fibroblasts
| PRJNA340482 | ENA
Project description:COPD is associated with disturbed tissue repair, possibly due to TGF-?-regulated miRNA changes in fibroblasts. Our aim was to identify TGF-?-regulated miRNAs and their differential regulation and expression in COPD compared to control fibroblasts. Small RNA sequencing was performed on TGF-?-stimulated and unstimulated lung fibroblasts from 15 COPD patients and 15 controls. Linear regression was used to identify TGF-?-regulated and COPD-associated miRNAs. Interaction analysis was performed to compare miRNAs that responded differently to TGF-? in COPD and control. Re-analysis of previously generated Ago2-IP data and Enrichr were used to identify presence and function of potential target genes in the miRNA-targetome of lung fibroblasts. In total, 46 TGF-?-regulated miRNAs were identified in COPD and 86 in control fibroblasts (FDR?<?0.05). MiR-27a-5p was the most significantly upregulated miRNA. MiR-148b-3p, miR-589-5p and miR-376b-3p responded differently to TGF-? in COPD compared to control (FDR?<?0.25). MiR-660-5p was significantly upregulated in COPD compared to control (FDR?<?0.05). Several predicted targets of miR-27a-5p, miR-148b-3p and miR-660-5p were present in the miRNA-targetome, and were mainly involved in the regulation of gene transcription. In conclusion, altered TGF-?-induced miRNA regulation and differential expression of miR-660-5p in COPD fibroblasts, may represent one of the mechanisms underlying aberrant tissue repair and remodelling in COPD.
| S-EPMC6890791 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis is a fatal interstitial lung disease characterized by the TGF-β (transforming growth factor-β)-dependent differentiation of lung fibroblasts into myofibroblasts, which leads to excessive deposition of collagen proteins and progressive scarring. We have previously shown that synthesis of collagen by myofibroblasts requires de novo synthesis of glycine, the most abundant amino acid found in collagen protein. TGF-β upregulates the expression of the enzymes of the de novo serine-glycine synthesis pathway in lung fibroblasts; however, the transcriptional and signaling regulators of this pathway remain incompletely understood. Here, we demonstrate that TGF-β promotes accumulation of ATF4 (activating transcription factor 4), which is required for increased expression of the serine-glycine synthesis pathway enzymes in response to TGF-β. We found that induction of the integrated stress response (ISR) contributes to TGF-β-induced ATF4 activity; however, the primary driver of ATF4 downstream of TGF-β is activation of mTORC1 (mTOR Complex 1). TGF-β activates the PI3K-Akt-mTOR pathway, and inhibition of PI3K prevents activation of downstream signaling and induction of ATF4. Using a panel of mTOR inhibitors, we found that ATF4 activation is dependent on mTORC1, independent of mTORC2. Rapamycin, which incompletely and allosterically inhibits mTORC1, had no effect on TGF-β-mediated induction of ATF4; however, Rapalink-1, which specifically targets the kinase domain of mTORC1, completely inhibited ATF4 induction and metabolic reprogramming downstream of TGF-β. Our results provide insight into the mechanisms of metabolic reprogramming in myofibroblasts and clarify contradictory published findings on the role of mTOR inhibition in myofibroblast differentiation.
| S-EPMC7605163 | biostudies-literature
Project description:Studies of miRNA association with Argonaute (AGO) proteins in mammalian cells have indicated lack of bias toward particular AGO. However, to our knowledge, the use of quantitative methods for studying miRNA association with different AGOs has not been reported so far. In this work we compared the total miRNA content in AGO1 and AGO2 immunoprecipitates obtained from MCF7 adenocarcinoma cells using TaqMan Low Density miRNA Arrays and successfully verified selected miRNAs with qPCR. For most of the miRNA species AGO1 and AGO2 profiles were well correlated, however, some miRNAs demonstrated consistent biases toward one of the Argonautes. Furthermore, miRNAs which were predominantly AGO2-associated derived mostly from sense strands of the corresponding pre-miRNAs while the majority of AGO1 biased miRNAs originated from antisense strands of the pre-miRNAs. Additionally, we show that circulating miRNA in human blood plasma can be immunoprecipitated with both AGO1 and AGO2 antibody. However, unlike in cell lysates, AGO1 and AGO2 associated miRNA profiles in plasma did not correlate, indicating that many cell types contribute to circulating miRNA (given that expression of AGO proteins is tissue specific). Furthermore, AGO-specific miRNA profiles in blood cells differed significantly from miRNAs profiles in plasma indicating that most circulating miRNAs are likely to derive from non-blood cells. Since circulating miRNAs hold great promise as biomarkers for numerous cancers and other diseases, we hypothesize that AGO-specific miRNA profiles might add an additional dimension to circulating miRNA-based diagnostics.
| S-EPMC3551861 | biostudies-other
Project description:Invasive lung adenocarcinoma (LADC) is classified histologically as lepidic, acinar, papillary, micropapillary, or solid. We found that A549 human LADC cells formed tumors with distinct histological features—solid-type or acinar-type tumors—depending on the site of development in immunodeficient mice and that a solid-to-acinar transition (SAT) could be induced by cancer-associated fibroblasts (CAFs) in 3D cocultures with A549. To clarify the molecular mechanisms contributing to SAT induction, we performed RNA-seq analysis of four A549 tumor cell samples derived from solid- or acinar-type tumor tissue formed in vivo or from 3D tumor colonies formed in the presence or absence of CAFs in vitro.
2022-03-15 | GSE169029 | GEO
Project description:Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Using an in-silico data-driven approach, we identified a robust connection between the transcriptomic perturbations in IPF disease and those induced by saracatinib, a selective Src kinase inhibitor, originally developed for oncological indications.We investigated the anti-fibrotic efficacy of saracatinib relative to nintedanib and pirfenidone in in vitro modele using normal human lung fibroblasts (NHLFs).
2022-08-30 | GSE178518 | GEO
Project description:To assess the transcriptomic response of human lung fibroblast to TGF-β, human MRC5 pulmonary fibroblasts (CCL-171) were exposed or not to TGF-β at 10 ng/mL. RNA samples were harvested 24 hours after TGF-β exposition. Three independent experiments were carried out.
2019-04-11 | GSE97829 | GEO
Project description:Lung fibroblasts play an important role in extracellular matrix homeostasis and this process is mainly regulated by transforming growth factor-beta (TGF-β). Hence, lung fibroblasts are postulated to play a crucial role in aberrant lung tissue repair and remodeling, which is a main factor in lung diseases like COPD. In this study, the effect of TGF-β1 on the miRNA expression in parenchymal lung fibroblasts is investigated.
2017-11-01 | GSE86185 | GEO
Project description:Most head and neck cancer (HNC) patients are resistant to cetuximab, an antibody against the epidermal growth factor receptor. Such therapy resistance is known to be mediated, in part, by stromal cells surrounding the tumor cells; however, the mechanisms underlying such a resistance phenotype remain unclear. To identify the mechanisms of cetuximab resistance in an unbiased manner, RNA-sequencing (RNA-seq) of HNC patient-derived xenografts (PDXs) was performed. Comparing the gene expression of HNC-PDXs before and after treatment with cetuximab indicated that the transforming growth factor-beta (TGF-beta) signaling pathway was upregulated in the stromal cells of PDXs that progressed on cetuximab treatment (CetuximabProg-PDX). However, in PDXs that were extremely sensitive to cetuximab (CetuximabSen-PDX), the TGF-beta pathway was downregulated in the stromal compartment. Histopathological analysis of PDXs showed that TGF-beta-activation was detected in cancer-associated fibroblasts (CAFs) of CetuximabProg-PDX. These TGF-beta-activated CAFs were sufficient to limit cetuximab efficacy in vitro and in vivo. Moreover, blocking the TGF-beta pathway using the SMAD3 inhibitor, SIS3, enhanced cetuximab efficacy and prevented the progression of CetuximabProg-PDX. Altogether, our findings indicate that TGF-beta-activated CAFs play a role in limiting cetuximab efficacy in HNC.
| S-EPMC7073231 | biostudies-literature
Project description:To assess the transcriptomic response of human lung fibroblast to TGF-β, human MRC5 pulmonary fibroblasts (CCL-171) were exposed to TGF-β at 10 ng/mL. RNA samples were harvested 24 hours after TGF-β exposition. Three independent experiments were carried out.
2019-04-11 | GSE97832 | GEO