Abstract | INTRODUCTION: METHODS: Since the amalgamation of clinical and laboratory data besides tumor histopathogenesis and transcriptional regulatory features of the tumor emerges to exhibit essential roles in the behavior and progression of prolactinomas; in this work, we integrated mRNA- and microRNA ( miRNA)-level transcriptome data that exploit disease-specific signatures in addition to biological and pharmacological data to elucidate a rational prioritization of pathways and drugs in prolactinoma. RESULTS: We identified 8 drug candidates through drug repurposing based on mRNA- miRNA-level data integration and evaluated their potential through in vitro assays in the MMQ cell line. Seven repurposed drugs including 5-fluorocytosine, nortriptyline, neratinib, puromycin, taxifolin, vorinostat, and zileuton were proposed as potential drug candidates for the treatment of prolactinoma. We further hypothesized possible mechanisms of drug action on MMQ cell viability through analyzing the PI3K/Akt signaling pathway and cell cycle arrest via flow cytometry and Western blotting. DISCUSSION: We presented the transcriptomic landscape of prolactinoma through miRNA and mRNA-level data integration and proposed repurposed drug candidates based on this integration. We validated our findings through testing cell viability, cell cycle phases, and PI3K/Akt protein expressions. Effects of the drugs on cell cycle phases and inhibition of the PI3K/Akt pathway by all drugs gave us promising output for further studies using these drugs in the treatment of prolactinoma. This is the first study that reports miRNA-mediated repurposed drugs for prolactinoma treatment via in vitro experiments.
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Authors | Busra Aydin, Sema Arslan, Fatih Bayraklı, Betul Karademir, Kazim Yalcin Arga |
Journal | Neuroendocrinology
(Neuroendocrinology)
Vol. 112
Issue 2
Pg. 161-173
( 2022)
ISSN: 1423-0194 [Electronic] Switzerland |
PMID | 33706313
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021 S. Karger AG, Basel. |
Chemical References |
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Topics |
- Drug Repositioning
- Humans
- MicroRNAs
- Prolactinoma
(drug therapy)
- RNA, Messenger
- Transcriptome
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