MicroRNA-137 inhibits pituitary prolactinoma proliferation by targeting AKT2

• Published in: Journal of endocrinological investigation Vol. 46; no. 6; pp. 1145 - 1154
• Main Authors: Xu, Q., Yu, Z. X., Xie, Y. L., Bai, L., Liang, S. R., Ji, Q. H., Zhou, J.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-06-2023; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; Adenoma; AKT protein; AKT2 protein; Animals; Brain tumors; Cell proliferation; Cell Proliferation - genetics; Cholecystokinin; Computational Biology; Down-regulation; Endocrinology; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genes; Genomes; Internal Medicine; Medical treatment; Medicine; Medicine & Public Health; Metabolic Diseases; Metastases; MicroRNAs; MicroRNAs - genetics; miRNA; Molecular modelling; Original Article; Phosphatidylinositol 3-Kinases; Pituitary; Pituitary Neoplasms - genetics; Prolactin; Prolactinoma - genetics; Proto-Oncogene Proteins c-akt - genetics; Rats; Tumorigenesis; Tumors; microRNAs; Bioinformatic; Aggressive prolactinomas
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-022-01964-7

Purpose
Prolactinoma is the most common type of pituitary adenoma. Most prolactinoma need medical treatment, but some of them are aggressive and require surgery. In previous decades, some miRNAs have been manifested as oncogenes or tumor suppressors. Consequently, miRNAs' abnormal expression involves tumorigenesis, invasion, and metastasis of different types of tumors, including pituitary tumors. The current study aim to explore the aggressiveness-associated miRNAs in prolactinoma and underlying molecular mechanisms based on the bioinformatic analysis and fundamental experiment studies.
Methods
GSE46294 miRNA expression profile from the Gene Expression Omnibus (GEO) database was downloaded. Differentially expressed miRNAs (DEMs) were filtered from this data. Subsequently, the target genes of downregulated miRNAs were analyzed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. RT-qPCR, western blot, and CCK-8 assays were used to validate the effect of miR-137 on the proliferation of MMQ cells through AKT2. Finally, the binding site of rat miR-137 to AKT2 were predicted by
Targetscan
and 
Bibiserv
database, and verified by double luciferase reporter assay.
Results
Twenty-four changed DEMs (fourteen upregulated and ten downregulated) were identified. Target genes of downregulated DEMs were classified into three groups by GO terms. KEGG pathway enrichment analysis revealed these target genes enriched in the PI3K-Akt pathway. We also confirmed that miR-137 can target AKT2 and inhibit the proliferation of MMQ cells induced by AKT2.
Conclusion
MiR-137 suppressed prolactinomas' aggressive behavior by targeting AKT2.