RETRACTED ARTICLE: The Downregulation of MicroRNA-146a Modulates TGF-β Signaling Pathways Activity in Glioblastoma

Abstract

Transforming growth factor-β (TGF-β) is considered to be one of the main factors responsible for glioblastoma tumorigenesis. MicroRNAs have recently been shown to regulate cell proliferation, differentiation, and apoptosis. However, the involvement of miRNA-146a in TGF-β1-induced glioblastoma development remains largely unknown. Here, miRNA-164a transfection was used to overexpress miRNA-164a in U87, and then real-time quantitative PCR and Western blot were applied to detect the gene transcription and protein expression. In addition, MTT and wound healing assay were also used to observe cell proliferation and migration. Our data revealed that miRNA-146a was downregulated by TGF-β1 treatment, but upregulated by miRNA-164a transfection. MiRNA-146a overexpression significantly reduced SMAD4 protein expression instead of p-SMAD2. Besides, miRNA-146a overexpression also decreased the messenger RNA (mRNA) and protein expression of epidermal growth factor receptor (EGFR) and MMP9 as well as the p-ERK1/2 level. Furthermore, the upregulation of miRNA-146a suppressed TGF-β1-mediated U87 proliferation and migration. These results demonstrate that miRNA-146a acts as a novel regulator to modulate the activity and transduction of TGF-β signaling pathways in glioblastoma, and the downregulation of miRNA-146a is required for overexpression of EGFR and MMP9, which can be considered an efficiently therapeutic target and a better understanding of glioblastoma pathogenesis.

Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo

“…[25][26][27]30 These activities suggest that miR-146a-PEINPs may inhibit renal fibrosis in patients with kidney disease. miR-146a has also been reported to suppress expression of …”

“…[25][26][27][28][29] Recently, miR-146a was reported to inhibit the TGF-β 1 -Smad signaling pathway by suppressing Smad4. 30 Increased miR-146a expression has been observed in kidney samples of diabetic nephropathy patients. 31 Based on these findings, we hypothesized that miR-146a might strongly inhibit renal fibrosis by inhibiting the TGF-β 1 -Smad signaling pathway and inflammation in the kidney.…”

“…30 qRT-PCR and immunofluorescence analysis showed that the expression of Smad4 mRNA and protein was higher in obstructed than in sham-operated kidneys ( Figure 8A and B). These increases were also significantly inhibited by miR-146a-PEI-NPs, but not by control-miR-PEI-NPs.…”

Up-regulation of miR-1825 inhibits the progression of glioblastoma by suppressing CDK14 though Wnt/β-catenin signaling pathway

“…Glioblastoma is the most common type of malignant primary intracranial tumor and is characterized by the hallmarks of cellular heterogeneity, rapid proliferation, angiogenesis, extensive invasion, hypoxia and necrosis [24,25]. It is an urgent need to gain deeper understanding of molecular mechanisms implicated in glioblastoma progression and development [26].…”

The role of micro-RNA in the regulation of signal pathways in gliomas

“…Так, было показано снижение уровня miR-146a в TGFb1-индуцированных клетках глиобластомы линии U87 [65]. MiR-146a ингибировала экспрессию SMAD4, но не pSMAD2, тем самым блокируя Smad-сигналинг.…”