MiRNA 34-a regulate SIRT-1 and Foxo-1 expression in endometriosis

Abstract

Purpose: The role of the Sirutin 1 (SIRT1) and MicroRNA-34 a (miR-34a) in endometriosis and the extent to which the miR-34a/SIRT1/p53 signaling pathway is involved in its pathogenesis is unclear, so we aimed to investigate the expression of miRNA 34-a, SIRT1, Forkhead boxO (FoxO-1), p53 and other apoptotic markers in endometrial tissue of women with endometriosis in order to better understand their role and the mechanisms of their actions in the pathogenesis of such disease and if it is related to apoptosis or not. Methods: Ectopic and eutopic endometriotic tissues were collected from seventy women with endometriosis while normal endometrial tissues were obtained from 40 fertile women without endometriosis and then gene expression of SIRT-1, miR-34a,p53, Bax, Bcl-2, Bcl-xL and FoxO-1 were measured using RT-PCR. Results: We detected that SIRT-1 and Bcl-xL genes expressions was significantly up-regulated while miRNA34-a,p53, Bax, Bcl-2 and FoxO-1 were down-regulated in endometrial tissue of endometriotic patients compared to that of those without endometriosis. There was an inverse relationship between SIRT-1a, Bcl-xL genes expressions and miR-34a, p53, Bax, Bcl-2 expressions as well as FoxO-1 expression. These results imply that miR-34a might regulate p53 through SIRT-1 and subsequently FoxO-1 expression in endometriotic tissue, and so it can contribute to the pathogenesis of endometriosis by decreasing the naturally occurring apoptosis in endometrium. Conclusion: This study may provide a potential biomarker for endometriosis therapeutics. Identification of target genes downstream of these transcriptional factors would allow better understanding of their respective roles in the pathogenesis of endometriosis.

Keywords

• SIRT1
• miR-34a
• p53
• Bax
• Bcl-2 and FoxO-1
• Endometriosis