Prolactinomas are the most common functional pituitary adenomas; the aggressive tumors still present challenge to clinicians. Aberrant expression of miRNAs has been functionally associated with prolactinomas. Here we explored the role of miR-137 on the proliferation, invasion and apoptosis of prolactinomas and its possible mechanism. Low expression of miR-137 was correlated with the invasive behavior of human prolactinomas and predicted high recurrence. MiR-137 inhibited cell proliferation, invasion and survivals of MMQ and GH3 cells and reduced tumor volume in F344 rat prolactinomas. The luciferase reporter assay confirmed that MITF was the direct target of miR-137. In addition, miR-137 mimics could inhibit MITF expression in vivo and in vitro. Upregulation of MITF expression promoted cell proliferation, invasion and survivals and reversed the anti-tumor effect of miR-137 in vivo and in vitro. Furthermore, miR-137 could also upregulate wnt-inhibitory factor-1 (WIF-1) and inhibit nuclear translocation of beta-catenin. Upregulation of WIF-1 with decitabine can enhance the inhibition on cell proliferation of miR-137. GSK-3 inhibitor, SB 216763, promoted cell proliferation by upregulation of total/cytoplasmic/nuclear beta-catenin and reversed tumor suppression of miR-137 mimics. Our data suggest that miR-137 possesses a tumor invasive suppressor function with a prognostic value in prolactinomas by targeting MITF and modulating Wnt-beta-catenin signaling pathway. Copyright © 2019 Endocrine Society.