- 作者：J. Browning Fitzgerald ; B.S.a ; Vargheese Chennathukuzhi ; Ph.D.a ; Faezeh Koohestani ; M.S.b ; Romana A. Nowak ; Ph.D.b ; Lane K. Christenson ; Ph.D.a ; lchristenson@kumc.edu
- 关键词：Leiomyoma ; microRNA ; miR-21 ; PDCD-4 ; uterine fibroids
- 刊名：Fertility and Sterility
- 出版年：2012
- 出版时间：September, 2012
- 年：2012
- 卷：98
- 期：3
- 页码：726-734.e2
- 全文大小：884 K
Objective
To 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.Design
Laboratory research.
Setting
Academic 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.