microRNA Determinants of Neuroendocrine Differentiation in Prostate Cancer
Abstract
We demonstrated that progression of advanced CRPC with adenocarcinoma characteristics (CRPC-Adeno) to therapy-induced, androgen-independent NE (CRPC-NE) states is associated with a characteristic set of miRNA alterations that promote plasticity of advanced prostate adenocarcinomas to NEPC (Bhagirath et al., Oncogene, 2020). Importantly, we could develop a 'novel miRNA classifier' to robustly stratify CRPC-NE tumors from CRPC Adenocarcinomas. Further validation of the classifier in clinical samples from two independent sites showed a '5-miRNA' classifier to be of significance in distinguishing between CRPC-Adenocarcinomas and CRPC-NE tumors. This classifier included downregulation of miR-28-3p as an important feature. In view of this data, we examined the functional role of miR-28-3p in prostate cancer. Our studies suggest that miR-28-3p plays a tumor suppressive role in advanced prostate cancer. We discovered that this miRNA directly represses Vimentin, a mesenchymal gene. Therefore, loss of this miRNA in advanced prostate cancer leads to the upregulation of Vimentin and induction of epithelial-to-mesenchymal transition (EMT), favoring tumor progression. Furthermore, this miRNA represses oncogenic Akt3-mediated signaling. In addition, we performed in vivo studies on miR-410 in prostate cancer. These studies demonstrated an oncogenic role of miR-410 in neuroendocrine prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2022
- Accession Number
- AD1202185
Entities
People
- Sharanjot Saini
Organizations
- Augusta University