Transforming growth factor-β (TGF-β) pathway plays crucial roles during the carcinogenesis and metastasis. TGF-β receptor 2 (TGFBR2) is a key molecule for the regulation of TGF-β pathway and frequently downregulated or lost in several cancer types including non-small cell lung cancer (NSCLC), and TGF-β pathway is often regulated by negative-feedback mechanisms, but little is known about the mechanism of TGFBR2 downregulation in NSCLC. Here, we found that the expression of miR-520e is upregulated in metastatic tumor tissues compared with non-metastatic ones, and its expression is inversely correlated with that of TGFBR2 in clinical samples. We also discovered that TGF-β dramatically increased the expression of miR-520e, which targeted and downregulated TGFBR2, and the suppression of miR-520e significantly impaired TGF-β-induced TGFBR2 downregulation. Chromatin immunoprecipitation–PCR experiments further showed that miR-520e is transcriptionally induced by SMAD2/3 in response to TGF-β. Our findings reveal a novel negative-feedback mechanism in TGF-β signaling and the expression level of miR-520e could be a predictive biomarker for NSCLC metastasis.
Aims It has been demonstrated that there are abundant stable microRNAs (miRNAs) in plasma, which is potentially disease‐specific. Adrenergic and muscarinic pathways play an important role in voiding physiology. Alterations in the levels of miRNAs are thought to influence the regulation of these pathways at the molecular level. The aim of this study was to investigate the relationship of miRNAs with overactive bladder pathogenesis and to provide a new perspective to treatment approaches. Methods This study included patients with an overactive bladder (OAB) diagnosis and a healthy control group. All patients completed a validated OAB‐V8 questionnaire. The relative expression levels of 12 miRNAs were examined in plasma by PCR. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic qualification of miRNAs. Results The relative expression levels of let‐7b‐5p, miR‐92a‐3p, miR‐98‐5p, miR‐142‐3p, and miR‐200c‐3p were significantly upregulated and miR‐139‐5p was significantly downregulated in patients with OAB and no correlation was determined between the levels of miRNAs with OAB symptom score. Among the miRNAs, miR‐98‐5p provided the highest diagnostic accuracy alone (area under curve [AUC] = 0.79) in ROC analysis. The combination of miR‐98‐5p + miR‐139‐5p was seen to be a good indicator (AUC = 0.839). Conclusions These results suggest that alteration of the miRNA levels can be used as auxiliary parameters to explain the pathophysiology of OAB syndrome and could shed light on new treatment options.
Background: Non-Small Cell Lung Cancer (NSCLC) is an aggressive cancer type due to high metastatic capacity. Nuclear Factor Kappa B (NF-κB) is a consistently active transcription factor in malignant lung cancer cells and has crucial significance in NSCLC progression. It is also implicated in the transcriptional regulation of many genes including microRNAs (miRNAs) that function as tumor suppressor or oncogene. It has been increasingly reported that several miRNAs defined as gene members are induced by NF-κB. The present study aimed to find novel miRNAs that are regulated by NF-κB. Methods: Chromatin İmmunoprecipitation Sequencing (ChIP-Seq) experiment and bioinformatic analysis were used to determine NF-κB-dependent miRNAs. Western blot analysis, quantitative real-time polymerase chain reaction (qRT-PCR), luciferase reporter gene assays were carried out to investigate the target genes of miRNAs. To determine biologic activity, transwell invasion and MTT assay were carried out on H1299 NSCLC cell line. miRNA expression level was evaluated in metastatic and non-metastatic tissue samples of NSCLC patients. Results: ChIP-Seq and qRT-PCR experiments showed that miR-548as-3p is transcriptionally regulated by NF- κB in response to Tumor Necrosis Factor-α (TNF-α) treatment. Then, we found that tumor suppressor Phosphatase and Tension homolog (PTEN) is a direct target of miR-548as-3p. Furthermore, miR-548as-3p mediates phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway and NF-κB-implicated genes including Matrix Metalloproteinases 9 (MMP9), Slug and Zeb1. We further showed that miR-548as-3p increased invasiveness of NSCLC cells and was upregulated in metastatic tumor tissues compared to non-metastatic ones. Conclusion: All these findings provide a miRNAs-mediated novel mechanism for NF-κB signaling and that miR-548as-3p could be a biomarker for NSCLC metastasis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.