Effects of microRNA-21 targeting PITX2 on proliferation and apoptosis of pituitary tumor cells

M. Cui, M. Zhang, H.-F. Liu, J.-P. Wang

Department of Neurology, The 5th Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. jianpingwang12@sina.com

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• Oncology

OBJECTIVE: Expression of pituitary homeobox 2 (PITX2) is significantly elevated in pituitary adenoma tissues, which also has lower microRNA (miR)-21 expression, indicating possible tumor-suppression role of miR-21. Bio-informatics analysis revealed targeting onto 3’-UTR of PITX2 by miR-21. This study aims to investigate the role of miR-21/PITX2 expression in proliferation and apoptosis of pituitary adenoma cells and pathogenesis.

PATIENTS AND METHODS: A total of 48 pituitary adenoma samples were collected in parallel with 12 normal brain tissues and were recruited in this study. Flow cytometry was employed to test Ki-67 expression and apoptosis. Expressions of miR-21 and PITX2 were compared, along with their targeted relationship by dual-luciferase reporter assay. Cultured HP75 cells were transfected with miR-21 mimic and/or si-PITX2. Caspase-3 activity was further quantified, followed by flow cytometry for apoptosis. MiR-21, cleaved caspase-3 and PITX2 expressions were tested.

RESULTS: Invasive pituitary adenoma tissues had significantly higher Ki-67 and PITX2, and lower miR-21 expressions or apoptosis than non-invasive tumors. MiR-21 targeted 3’-UTR of PITX2 gene to inhibit its expression. Elevated miR-21 and/or silencing PITX2 significantly depressed PITX2 expression in HP75 cells, potentiating caspase-3 activity, decreasing cell proliferation and facilitating apoptosis.

CONCLUSIONS: MiR-21 was down-regulated while PITX2 was up-regulated in pituitary adenoma tissues. MiR-21 can inhibit pituitary adenoma cell HP75 proliferation and facilitate apoptosis via inhibiting PITX2 expression.

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