lancet-header

Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.

Decreased MicroRNA-125b-5p Disrupts Follicle Steroidogenesis Through Targeting Pak3/ERK Signaling in Polycystic Ovary Syndrome

31 Pages Posted: 4 Feb 2019

See all articles by Xiaoqian Zhang

Xiaoqian Zhang

Nanjing Medical University - State Key Laboratory of Reproductive Medicine

Hua Xiao

Nanjing Medical University - Department of Obstetrics and Gynecology

Qiukai E

Nanjing Medical University - State Key Laboratory of Reproductive Medicine

Xuefeng Gong

Nanjing Medical University - State Key Laboratory of Reproductive Medicine

Xiaoyan Ying

Nanjing Medical University, Second Affiliated Hospital, Department of Obstetrics and Gynecology; Nanjing Medical University, Sir RunRun Hospital, Department of Obstetrics and Gynecology

Boqun Xu

Nanjing Medical University, Second Affiliated Hospital, Department of Obstetrics and Gynecology; Nanjing Medical University, Sir RunRun Hospital, Department of Obstetrics and Gynecology

Xiaoqiu Liu

Nanjing Medical University - Key Laboratory of Pathogen Biology of Jiangsu Province; Nanjing Medical University - Department of Microbiology

Xuesen Zhang

Nanjing Medical University - State Key Laboratory of Reproductive Medicine

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

undefined

Suggested Citation

Zhang, Xiaoqian and Xiao, Hua and E, Qiukai and Gong, Xuefeng and Ying, Xiaoyan and Xu, Boqun and Liu, Xiaoqiu and Zhang, Xuesen, Decreased MicroRNA-125b-5p Disrupts Follicle Steroidogenesis Through Targeting Pak3/ERK Signaling in Polycystic Ovary Syndrome (January 31, 2019). Available at SSRN: https://ssrn.com/abstract=3327344 or http://dx.doi.org/10.2139/ssrn.3327344

Xiaoqian Zhang

Nanjing Medical University - State Key Laboratory of Reproductive Medicine

Nanjing
China

Hua Xiao

Nanjing Medical University - Department of Obstetrics and Gynecology

Nanjing
China

Qiukai E

Nanjing Medical University - State Key Laboratory of Reproductive Medicine

Nanjing
China

Xuefeng Gong

Nanjing Medical University - State Key Laboratory of Reproductive Medicine

Nanjing
China

Xiaoyan Ying

Nanjing Medical University, Second Affiliated Hospital, Department of Obstetrics and Gynecology

Nanjing
China

Nanjing Medical University, Sir RunRun Hospital, Department of Obstetrics and Gynecology

Nanjing
China

Boqun Xu

Nanjing Medical University, Second Affiliated Hospital, Department of Obstetrics and Gynecology ( email )

Nanjing
China

Nanjing Medical University, Sir RunRun Hospital, Department of Obstetrics and Gynecology

Nanjing
China

Xiaoqiu Liu

Nanjing Medical University - Key Laboratory of Pathogen Biology of Jiangsu Province ( email )

Nanjing
China

Nanjing Medical University - Department of Microbiology ( email )

Nanjing
China

Xuesen Zhang (Contact Author)

Nanjing Medical University - State Key Laboratory of Reproductive Medicine ( email )

Nanjing
China

0 References

    0 Citations

      Click here to go to TheLancet.com

      Paper statistics

      Downloads
      45
      Abstract Views
      515
      PlumX Metrics
      Plum Print visual indicator of research metrics
      • Usage
        • Abstract Views: 493
        • Downloads: 45
      • Captures
        • Readers: 1
      see details