Circ_0047339 promotes the activation of fibroblasts and affects the development of urethral stricture by targeting the miR-4691-5p/TSP-1 axis
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ABSTRACT:
PROVIDER: PRJNA863103 | ENA |
REPOSITORIES: ENA
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Project description:Background: Urethral stricture is related to scar tissue fibrosis, but its pathogenesis is still unclear. This study aims to explore the mechanism of circular RNA (circRNA) in the occurrence and development of urethral stricture. Methods: CircRNA microarray was employed to analyze circRNA expression profiles between human urethral scar tissue and normal urethral tissue. The first nine circRNA differentially expressed were selected for RT-qPCR detection. Urethral scar fibroblasts were isolated from human urethral scar tissue and cultured in vitro. The cells were transfected with si-circ_0047339, LV-circ_0047339, and miR-4691-5p mimic and their corresponding negative controls. Related gene and protein expression was measured by RT-qPCR, Western Blot and immunofluorescence staining, and the cell function was detected by CCK-8 and EDU assay. The targeting relationship between miR-4691-5p and circ_0047339 or TSP-1 was analyzed by dual-luciferase reporter assay. Results: The results of circRNA microarray showed that there were 268 differential genes between urethral scar tissue and normal urethral tissue (circRNA expression difference multiple ≥2 and p value≤0.05). The enrichment analysis of KEGG (Kyoto encyclopedia of genes and genomes) showed that these circRNAs were significantly correlated with ECM-receptor interaction. The first nine differentially expressed circRNA were selected to predict the circRNA-miRNA network. RT-qPCR results showed that circ_0047339 was upregulated considerably in urethral scar tissue. After silencing circ_0047339, the proliferation of urethral scar cells decreased significantly, and the expression of collagen 1 (COL-1) and α-smooth muscle actin (α-SMA) also reduced. Circ_0047339 as a competing endogenous RNA (ceRNA) could increase the expression of TSP-1 by competitively binding miR-4691-5p. In addition, miR-4691-5p mimic transfection could inhibit the proliferation of urethral scar fibroblasts and the presentation of thrombospondin-1 (TSP-1), α-SMA and COL-1, while circ_0047339 overexpression eliminated this inhibition. Conclusion: Our results showed that the dysfunctional circ_0047339 might promote the growth and fibrosis of urethral scar fibroblasts through the ceRNA mechanism, thus promoting the development of urethral stricture via miR-4691-5p/TSP-1 axis.
2022-07-30 | GSE209937 | GEO
Project description:Urethral stricture is related to scar tissue fibrosis, but its pathogenesis is still unclear. This study aims to explore the regulatory mechanism of circular RNA (circRNA) in the occurrence and development of urethral stricture. CircRNA microarray was employed to analyze circRNA expression profiles between human urethral scar tissue and normal urethral tissue. The results of circRNA microarray showed that there were 296 differentially expressed genes between urethral scar tissue and normal urethral tissue. The enrichment analysis of Kyoto encyclopedia of genes and genomes showed that these circRNAs were significantly correlated with ECM-receptor interaction. The first nine differentially expressed circRNA were selected to predict the circRNA-miRNA network. RT-qPCR results showed that circ_0047339 was upregulated considerably in urethral scar tissue. Urethral scar fibroblasts were isolated from human urethral scar tissue and cultured in vitro. After silencing circ_0047339, the proliferation of urethral scar cells decreased significantly, and the expressions of Collagen I (COL-1) and α-smooth muscle actin (α-SMA) also reduced. As a competing endogenous RNA, circ_0047339 could increase the expression of TSP-1 by competitively binding miR-4691-5p. In addition, miR-4691-5p mimic transfection could inhibit the proliferation of urethral scar fibroblasts and the presentation of thrombospondin-1 (TSP-1), α-SMA and COL-1, while circ_0047339 overexpression eliminated this inhibition. Our results showed that circ_0047339 might promote the growth and fibrosis of urethral scar fibroblasts through miR-4691-5p/TSP-1 axis, thus promoting the development of urethral stricture.
| S-EPMC9428161 | biostudies-literature
Project description:This is a prospective-retrospective study to determine if the expression of the miRNA’s miR-31-3p and miR-31-5p are prognostic of patient outcomes or predictive of the benefit from anti-EGFR therapy in stage III Colon Cancer. The present study will utilize FFPE tumor samples collected from patients enrolled in the PETACC-8 study conducted by the Fédération Francophone de Cancérologie Digestive (FFCD). This phase 3 clinical trial prospectively randomized fully resected stage III colon cancer patients to receive adjuvant treatment with either FOLFOX-4 plus cetuximab or FLOFOX-4 alone.
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Project description:miR-493-5p, miR-3662, and miR-589-3p were estimated as working microRNAs in bleomycin- and methotrexate-induced phenotypic changes in A549 cells via microRNAs-Proteins Analysis of Integrative Relationship (miR-PAIR). To verify the effect of these miRNAs on the their target protein expression levels, comprehensive expression of proteins in A549 cells treated with miR-493-59, miR-3662, and miR-589-3p mimic was examined by SWATH-MS method. As expected by a miR-PAIR mehtod, almost target proteins were succesfully regulated by miR-493-5p and miR-589-3p mimics.
2025-07-25 | PXD053397 | Pride
Project description:Background : In lactating cow, a sunflower oil supplementation modulated the milk composition and the mammary genes expression whose mechanisms of regulations are unclear. Results : This lipid supplementation provoke, in mammary gland, the down regulation of microRNA miR-20a-5p and miR-142-5p, which are predicted to target genes previously determined as differentially expressed including those involved in lipid metabolism. Conclusion : Those two miRNA are good candidates to explain lipogenic genes regulations after sunflower oil supplementation. Significance : The current study clarified the nutriregulation of miRNA in the mammary gland. MiRNomes obtained by NGS sequencing of mammary gland of Holstein cows at the peak of lactation received a low forage diet supplemented or not with 4% of sunflower oil were compared. MiRNA differentially expressed confirmed by RT-qPCR were related to differentially expressed genes list previously identified in the same samples.
2016-07-01 | E-GEOD-81616 | biostudies-arrayexpress
Project description:MiRNAs have been shown to alter both protein expression and secretion in different cellular contexts. By combining in vitro, in vivo and in silico techniques, we demonstrated that overexpression of pre-miR-1307 reduced the ability of breast cancer cells to induce endothelial cell sprouting and angiogenesis. However, the molecular mechanism behind this and the effect of the individual mature miRNAs derived from pre-miR-1307 on protein secretion and is largely unknown. Here, we overexpressed miR-1307-3p|0, -3p|1 and 5p|0 in MDA-MB-231 breast cancer cells and assessed the impact of miRNA overexpression on protein secretion by Mass Spectrometry. Unsupervised hierarchical clustering revealed a distinct phenotype induced by overexpression of miR-1307-5p|0 compared to the controls and to the 5’isomiRs derived from the 3p-arm. Together, our results suggest different impacts of miR-1307-3p and miR-1307-5p on protein secretion which is in line with our in vitro observation that miR-1307-5p, but not the isomiRs derived from the 3p-arm reduce endothelial cell sprouting in vitro. Hence these data support the hypothesis that miR-1307-5p is at least partly responsible for impaired vasculature in tumors overexpressing pre-miR-1307.
2024-12-11 | PXD041087 | Pride
Project description:In urethral damage/stricture prevention, open and harsh urethral microenvironments as well as the isotropic compression and swelling properties of exogenous implants render urethral repair intractable. Here, a dynamically urethra-adapted and obligation-oriented trilayer hydrogel was constructed for integrated scarless urethral repair. The bottom diethylacrylamide -hydroxyethylacrylamide (D-H) hydrogel featuring high anti-fouling performance, the upper swellable verteporfin (VP)-loaded N,N'-methylenebisacrylamide-poly (N-isopropylacrylamide) (BP) with a hydrophilic Janus surface promote urethral regeneration through expediting cell migration and proliferation and the rigid and water-resistant Zein middle layer opposes urine voiding-arised BP shedding and resists inward BP swelling-driven urethral occlusion and urine permeation. Importantly, systematic proteomic and genomic analyses revealed that such hydrogel scaffolds expedite regeneration, alleviate inflammation and regulate extracellular matrix secretion, where BP swelling-induced outgrowth for fibrosis and scar formation is significantly inhibited by VP through the blockade of the scar-associated YAP signaling pathway. These microenvironment-adaptable design concepts provide a rationale for engineering urethral regeneration scaffolds.
2025-07-01 | GSE301213 | GEO
Project description:Post-transcriptional regulation of gene expression by miRNAs likely makes significant contributions to mRNA abundance at the embryo-maternal interface. In this study, we investigated how miR-26a-5p and miR-125b-5p contribute to molecular changes occurring in the uterine luminal epithelium, which serves as the first site of signal exchange between the mother and developing embryo. To measure de novo protein synthesis after miRNA delivery to primary uterine luminal epithelial cells, we employed pulsed stable isotope labeling by amino acids (pSILAC). We found that both miRNAs alter the proteome of luminal epithelial cells, impacting numerous cellular functions, immune responses, as well as intracellular and second messenger signaling pathways. Additionally, we identified several features of miRNA-mRNA interactions that may influence the targeting efficiency of miR-26a-5p and miR-125b-5p. Overall, our study suggests a complex interaction of miR-26a-5p and miR-125b-5p with their respective targets. However, both appear to cooperatively function in modulating the cellular environment of the luminal epithelium, facilitating the morphological and molecular changes that occur during the intensive communication between the embryo and uterus at pregnancy.
2025-05-07 | PXD056243 | Pride