Figure 2.

A schematic diagram of the role of various ncRNAs in modulating the TGF-β/SMAD signaling pathway in pituitary gland tumors. According to this cascade, it could be triggered through the binding of active TGF-β with TβRII and forming the TβRI-TβRII heteromeric complex, resulting in phosphorylation of Smad2/3, oligomerization with Smad4, and consequent nuclear translocation to modulate the transcription of ECM genes. Furthermore, Smad7 could play a remarkable role as a negative modulator of the TGF-β cascade. In addition, TGF-β has a significant part in triggering the activation of downstream signaling pathways containing MAPK, modulated by the Ras-Raf-MEK-ERK cascade, and TAK1, regulated by the TAB1 pathway. This could also lead to mediating the activation of MKK4-JNK and MKK3-p38 cascades and upregulation of AP-1 and ATF-2, respectively, and the overexpression of NF- κB to modulate profibrotic responses [61]. Previous studies have authenticated that several ncRNAs could have a significant part in regulating the TGF-β/SMAD cascade in pituitary gland tumors. As an illustration, recent literature has detected that overexpression of lnc-SNHG1 could considerably elevate the expression level of TβRII through activating TβRII/SMAD3 in invasive pituitary tumor cells via sponging miR-302/372/373/520 [31]. Furthermore, other research has indicated that upregulation of miR-93-5p could downregulate the expression level of Smad7, thereby activating the TGF-β1/Smad3 signaling-mediated fibrosis of prolactinoma cells [51]. Green arrows indicate the upregulation of target genes modulated via ncRNAs (miRNAs and lncRNAs); red arrows depict inhibition regulated by them.