• J Browning Fitzgerald, Vargheese Chennathukuzhi, Faezeh Koohestani, Romana A Nowak, and Lane K Christenson.
• Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
• Fertil. Steril. 2012 Sep 1; 98 (3): 726-734.e2.

ObjectiveTo determine whether programmed cell death 4 (PDCD-4) is altered in autologous leiomyoma and myometrial tissues and what microRNA-21's (miR-21) role is in PDCD-4 expression, apoptosis, and translation.DesignLaboratory research.SettingAcademic medical center.Patient(S)Myometrial and leiomyoma tissues from patients with symptomatic leiomyomata.Intervention(S)Tissue analysis and miR-21 knockdown in cultured immortalized myometrial (UtM) and leiomyoma (UtLM) cells.Main Outcome Measure(S)MiR-21 and PDCD-4 mRNA and protein expression.Result(S)Leiomyoma tissues robustly expressed the full-length 51 kd isoform of PDCD-4, but normal myometrial tissue had negligible expression. Consistent with autologous tissues, UtLM cells expressed elevated miR-21 and a similar pattern of PDCD-4 compared with UtM cells. Knockdown of miR-21 increased PDCD-4 levels in UtM cells and UtLM cells, indicating that it can regulate PDCD-4 expression. Loss of miR-21 also increased cleavage of caspase-3 (apoptosis marker) and increased phosphorylation of elongation factor-2 (marker of reduced translation) in both cell lines.Conclusion(S)Elevated leiomyoma miR-21 levels are predicted to decrease PDCD-4 levels, thus leiomyomas differ from other tumors where loss of PDCD-4 is associated with tumor progression. Our studies indicate regulation of PDCD-4 expression is not a primary miR-21 function in leiomyomas, but instead miR-21 is able to impact cellular apoptosis and translation, through unknown targets, in a manner consistent with its involvement in the pathophysiology of uterine fibroids.Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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