MiRNA-34a reversed TGF-β-induced epithelial-mesenchymal transition via suppression of SMAD4 in NPC cells

In this study, we found that transforming growth factor-β (TGF-β), which reportedly promotes EMT in multiple cancers, can trigger EMT and increase the invasive and migratory capacities of NPC cells. Conversely, the downregulation of SMAD4, a vital member of the canonical TGF-β pathway, reversed the TGF-β-induced EMT, invasion, and migration. Further experiments revealed that SMAD4 was the target of miRNA-34a, which was downregulated in NPC tissues and suppressed NPC cell metastasis in vivo. miRNA-34a overexpression also antagonized the TGF-β-induced EMT progression, invasion, and migration through SMAD4 inhibition. However, the restoration of SMAD4 expression rescued the inhibitory effects of miRNA-34a on tumorigenesis. All these results confirmed that miRNA-34a suppressed the TGF-β-induced EMT, invasion, and migration of NPC cells by directly targeting SMAD4, which indicated the potential of miR-34a as a therapeutic target against NPC.Graphical abstractTGF-β signaling is initiated by the cytokine’s binding to its receptor, leading to the phosphorylation of SMAD2 and SMAD3 and formation of the SMAD protein complexes with SMAD4. The complexes subsequently translocate to the nucleus and interact with some transcription factors, which may contribute to EMT. MiR-34a, downregulted in NPC tissues, suppresses the TGF-β-induced EMT, invasion, and migration of NPC cells by directly targeting SMAD4. Together, these findings indicate the potential of miR-34a as a therapeutic t...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research