Lineage-dependent role of miR-410-3p as oncomiR in gonadotroph and corticotroph pituitary adenomas or tumor suppressor miR in somatotroph adenomas via MAPK, PTEN/AKT, and STAT3 signaling pathways

• Published in: Endocrine Vol. 65; no. 3; pp. 646 - 655
• Main Authors: Grzywa, Tomasz M., Klicka, Klaudia, Rak, Beata, Mehlich, Dawid, Garbicz, Filip, Zieliński, Grzegorz, Maksymowicz, Maria, Sajjad, Emir, Włodarski, Paweł K.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2019; Springer Nature B.V
• Subjects: Adenoma; AKT protein; Brain tumors; Cell proliferation; Cyclin B1; Cyclin D1; Diabetes; Endocrinology; Humanities and Social Sciences; Internal Medicine; Invasiveness; MAP kinase; Medicine; Medicine & Public Health; multidisciplinary; Original; Original Article; Pituitary; Pituitary (anterior); PTEN protein; Ribonucleic acid; RNA; Science; Signal transduction; Stat3 protein; Transfection; Tumor suppressor genes; Tumors; PTEN; miR-410-3p; MicroRNA; Proliferation; Invasiveness; Pituitary adenoma
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-019-01960-7

Purpose miR-410-3p plays opposite roles in different cancers and may act as an oncomiR or tumor suppressor miR. The purpose of this study was to assess the role of miR-410-3p in somatotroph, gonadotroph, and corticotroph pituitary adenomas. Methods Tissue samples were obtained from 75 patients with pituitary adenoma. miR-410-3p expression was assessed using qRT-PCR performed on RNA isolated from fresh frozen samples. In vitro experiments were performed on cell lines derived from somatotroph (GH3), gonadotroph (RC-4B/C), and corticotroph (AtT-20) pituitary tumors. Cells were transfected with synthetic mimic of miR-410-3p or non-targeting scrambled-miR control. Subsequently, proliferation assays and transwell invasion assays were performed. The expression of cyclin D1, E1, and B1 in cells after transfection was determined using qRT-PCR. The activation of MAPK, PTEN/AKT and STAT3 signaling pathways were assessed using western blot. Results We have found that the level of expression of miR-410-3p differs in particular types of pituitary adenomas. miR-410-3p significantly upregulates proliferation and invasiveness of RC-4B/C and AtT-20 cells, while inhibiting GH3 cells. We observed that the levels of cyclin B1 upon transfection with miR-410-3p mimic were increased in RC-4B/C and AtT-20, yet decreased in GH3 cells. We have shown that miR-410-3p promoted the activation of MAPK, PTEN/AKT, and STAT3 signaling pathways in RC-4B/C and AtT-20 cells, but suppressed their activity in GH3 cells. Conclusions miR-410-3p acts as an oncomiR in gonadotroph and corticotroph adenoma cells, while as a tumor suppressor miR in somatotroph adenoma cells.