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.

journal_name

Mol Cell Endocrinol

authors

Wei D,Yu Z,Cheng Y,Jiawei H,Jian G,Hua G,Guilan D

doi

10.1016/j.mce.2020.111083

subject

Has Abstract

pub_date

2021-01-15 00:00:00

pages

111083

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(20)30385-3

journal_volume

520

pub_type

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