miR-93-5p targets Smad7 to regulate the transforming growth factor- β1/Smad3 pathway and mediate fibrosis in drug-resistant prolactinoma.

miR-93-5p targets Smad7 to regulate the transforming growth factor-β1/Smad3 pathway and mediate fibrosis in drug-resistant prolactinoma. Brain Res Bull. 2019 Apr 01;: Authors: Hu B, Mao Z, Du Q, Jiang X, Wang Z, Xiao Z, Zhu D, Wang X, Zhu Y, Wang H Abstract Prolactinoma is a common subtype of pituitary tumors. Dopamine receptor agonists are the preferred treatment for prolactinoma; however, with this therapy, drug resistance often occurs. In our previous work, we found that partial resistant prolactinomas showed increased fibrosis and that the transforming growth factor (TGF)-β1/Smad3 signaling pathway mediated fibrosis and was involved in drug resistance. Additionally, the success of surgery is known to be heavily influenced by the consistency of the pituitary adenoma. Therefore, in this study, we aimed to clarify the mechanisms of fibrosis in prolactinoma. Using high-throughput sequencing for analysis of microRNAs, we found that miR-93-5p was significantly upregulated in prolactinoma samples with a high degree of fibrosis compared with that in samples without fibrosis. Furthermore, we found that miR-93-5p was negatively correlated with the relative expression of Smad7 and positively correlated with the relative expression of TGF-β1 in clinical prolactinoma samples. In addition, luciferase reporter assays showed that miR-93-5p could downregulate the Smad7 gene, an important inhibitor of the TGF-β1/Smad3 signaling pathway, and ac...
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research