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Overexpression of miR-144-3p alleviates polycystic ovaries syndrome through targeting expression of HSP-70

Gene Therapy volume 29, pages 217–226 (2022)Cite this article

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Abstract

Increasing microRNAs are shown to be participate in polycystic ovarian syndrome (PCOS) pathogenesis. Nevertheless, the biological effects of miR-144-3p and its detailed mechanisms in PCOS are to be investigated. The purpose of our work was to study the function of miR-144-3p in PCOS. Currently, Expression of miR-144-3p was greatly reduced in PCOS patients and PCOS rat models. In addition, HSP-70 expression was greatly elevated PCOS. Cell proliferation assays and flow cytometry assay were carried out following the overexpression of miR-144-3p in ovarian granulosa cells from PCOS rat models. We observed that miR-144-3p overexpression induced the proliferation and repressed cell apoptosis while loss of miR-144-3p demonstrated an opposite process. Then, PCOS rat models were classified to four groups: LV-NC group, LV-miR-144-3p group, Anti-control group, and Anti-miR-144-3p group. In response to loss of miR-144-3p, we found E2, T, and LH serum levels were elevated and FSH serum level was inhibited. Upregulation of miR-144-3p exhibited an opposite process. Moreover, HSP-70 was a direct target of miR-144-3p. Furthermore, increased expression of HSP-70 rescued the effects of miR-144-3p on ovarian granulosa cell growth and apoptosis. In addition, knockdown of HSP-70 alleviated endocrine disorders and abnormal ovarian weight in vivo. To sum up, miR-144-3p might function as a novel target for PCOS treatment via targeting HSP-70.

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Fig. 1: miR-144-3p level was reduced in ovarian cortex tissues and serums of PCOS patients.
Fig. 2: Establishment of rat models of PCOS.
Fig. 3: HSP-70 level was induced in ovarian cortex tissues and PCOS patients and rats models.
Fig. 4: The effect of miR-144-3p on the ovarian granulosa cells viability and apoptosis.
Fig. 5: The effect of miR-144-3p on the endocrine in PCOS rat models.
Fig. 6: HSP-70 was a direct target of miR-144-3p.
Fig. 7: The effect of HSP-70 on the ovarian granulosa cells viability and apoptosis.
Fig. 8: The effect of HSP-70 on the endocrine in PCOS rat models.

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The data are available upon reasonable request.

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Funding

This work was supported by National Key Research and Development Program of China [Grant No. 2018YFC1002804 and No. 2016YFC1000600], National Natural Science Foundation of China [Grant No. 81571513, No. 81771662, No. 81771618 and No. 81801540], and the Major Technological Innovation Projects in Hubei Province [Grant No. 2017ACA101].

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Author notes

  1. These authors contributed equally: Bing Qu, Qinghong Zhao

Authors and Affiliations

  1. Department of Reproductive Medicine Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, 430060, PR China

    Bing Qu, Xueyao Li & Jing Yang

  2. Ultrasound Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China

    Qinghong Zhao

  3. Department of Obstetrics and Gynecology, Union Wuhan Red Cross Hospital (Red Cross Hospital of Wuhan), Wuhan, 430015, China

    Qinglian Ma

  4. Department of Medical Technology, China Resources Wisco General Hospital, Wuhan, 430080, PR China

    Tian Yang

  5. Reproductive Medicine Center, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430015, China

    Yu Chen

  6. Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China

    Yan Zhang

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Contributions

JY and YZ designed the work; BQ and QZ performed the experiments; QM, TY, and XL collected the data and did the analysis; YC contributed essential reagents or tools; BQ drafted the manuscript; All of the authors approved the final version.

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Correspondence to Jing Yang or Yan Zhang.

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Qu, B., Zhao, Q., Ma, Q. et al. Overexpression of miR-144-3p alleviates polycystic ovaries syndrome through targeting expression of HSP-70. Gene Ther 29, 217–226 (2022). https://doi.org/10.1038/s41434-020-00191-0

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