Dysregulated miR-137 and its target EGFR contribute to the progression of pituitary adenomas.

Abstract

Pituitary adenomas (PAs) hypersecrete hormones or cause mass effect symptoms, with 10%-35% patients showing resistance to standard therapies. Targeting epidermal growth factor receptor (EGFR) has significantly improved the clinical outcome in many cancers. In this study, immunochemistry results showed that EGFR associated H-scores in 116 PA samples were higher than those in pituitary glands, and that p21, p27-and Wif-1 associated H-scores were lower (P < 0.05 for all). Patients with high levels of EGFR had increased PA invasion, lower total resection, and lower p21 and p27 expression than those with low levels of EGFR expression. Dual-luciferase reporter gene assays showed that EGFR was the target gene of miR-137, and miR-137 mimic could inhibit the cell proliferation of GH3 cells and induce apoptosis and G1-phase arrest of GH3 cells. A combination of miR-137 mimic and AZD9291 had stronger inhibition on GH3 cells compared with miR-137 mimic or AZD9291 alone; furthermore, miR-137 inhibitor partially reversed the inhibition of AZD9291. p21 and p27 were shown to be involved in the miR-137- and AZD9291-mediated effects on GH3 cells. In all, activation of EGFR in PAs was related to tumor invasive behavior, which reduced the total resection of PAs in patients. A combination of miR-137 and AZD9291 provided a potential treatment for PAs, especially for patients who show resistance to standard treatment.

• Authors: Dong Wei, Zhang Yu, Yue Cheng, Huang Jiawei, Gao Jian, Gao Hua, Dong Guilan
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 520 Pg. 111083 (01 15 2021) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 33246030 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Acrylamides
• Aniline Compounds
• MIRN137 microRNA, human
• MicroRNAs
• osimertinib
• EGFR protein, human
• ErbB Receptors

Topics

• Acrylamides (pharmacology)
• Adenoma (genetics, pathology)
• Adolescent
• Adult
• Aged
• Aniline Compounds (pharmacology)
• Cell Line, Tumor
• Disease Progression
• ErbB Receptors (genetics, metabolism)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Logistic Models
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Multivariate Analysis
• Neoplasm Invasiveness
• Pituitary Neoplasms (genetics, pathology)
• Young Adult