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Decreased MicroRNA-125b-5p Disrupts Follicle Steroidogenesis Through Targeting Pak3/ERK Signaling in Polycystic Ovary Syndrome
31 Pages Posted: 4 Feb 2019
More...Abstract
Background/Aims: Disrupted androgen and estrogen synthesis is considered as the most common characteristics in polycystic ovary syndrome (PCOS). However, the mechanisms underlying the alteration in steroidogenesis in the ovaries of PCOS patients remain elusive.
Methods and Results: qRT-PCR analysis showed that miR-125b-5p was significantly downregulated in the sera of PCOS patients. In mouse preantral follicles, inhibiting miR-125b-5p upregulated the expression of androgen synthesis-related genes and stimulated secretion of testosterone, while downregulated estrogen synthesis-related genes and decreased estradiol release. In contrast, overexpression of miR-125b-5p reversed these steroidogenesis-related gene expression and hormone release. Mechanistic studies identified Pak3 as a direct target of miR-125b-5p. Furthermore, inhibiting miR-125b-5p facilitated the activation of ERK1/2 in mouse preantral follicle, while inhibiting Pak3 abrogated this activating effect. Of note, inhibiting Pak3 antagonized the promoting effect of miR-125b-5p inhibitor on the expression of androgen synthesis-related enzymes and testosterone secretion.
Conclusion: Due to the decreased miR-125b-5p expression, Pak3 expression was markedly increased in the ovaries of PCOS patients, leading to activation of ERK signaling, thus stimulating the expression of androgen synthesis-related enzymes and testosterone secretion in hyperandrogenic PCOS (HA-PCOS) patients. Our study provided a potential significance of miR-125b-5p/Pak3/ERK axis as new biomarkers of HA-PCOS.
Funding: This work was supported by National Key Research and Development Program of China (2018YFC1003703, 2018YFC1004203), National Natural Science Foundation of China (81501797 to X.Q.L.; 81873820 to B.Q.X.), the Key University Natural Science Research Project of Jiangsu Province (15KJA320003 to X.S.Z.), Jiangsu Six Talent Peaks Project to X.S.Z., State Key Laboratory of Reproductive Medicine (SKLRM-KA201605 to B.Q.X.).
Declaration of Interest: All authors declare that they have no conflict of interests.
Ethical Approval: This study was approved by the Ethics Committee of the Second Affiliated Hospital of Nanjing Medical University.
Keywords: miR-125b-5p, steroidogenesis, Pak3, PCOS
Suggested Citation: Suggested Citation