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MiR-93 Inhibits Trophoblast Cell Proliferation and Promotes Cell Apoptosis by Targeting BCL2L2 in Recurrent Spontaneous Abortion

Reproductive Sciences volume 27, pages 152–162 (2020)Cite this article

Abstract

Recurrent spontaneous abortion (RSA) is a common health problem that affects 1–5% of women in reproductive age. Plenty of studies have indicated that microRNAs (miRNAs) are involved in the occurrence of miscarriage. MiR-93 has a wide range of functions in mammalian tissues and plays an important role in many diseases especially for cancers. However, it remains unknown whether miR-93 is associated with human RSA. In this report, clinical samples revealed that miR-93 expression was significantly elevated in the villi tissues of RSA patients. Upregulation of miR-93 inhibited human trophoblast cells HTR-8/SVneo cell proliferation, migration, and invasiveness, but promoted cell apoptosis in vitro. Conversely, the downregulation of miR-93 reversed these effects. Bcl-2 like protein 2 (BCL2L2), a potential target gene of miR-93, was inversely correlated with miR-93 expression in the villi of clinical samples. Furthermore, the luciferase reporter system demonstrated that miR-93 directly downregulated the expression of BCL2L2 by binding a specific sequence of its 3′-untranslated region (3′UTR). Collectively, these data strongly suggest that miR-93 regulates trophoblast cell proliferation, migration, invasive, and apoptosis by targeting BCL2L2 expression and is involved in the pathogenesis of RSA.

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Funding

This work was supported by grants from The National Key Research and Development Program of China (2016YFC1000307), the National Natural Science Foundation of China (No. 81771590), and CAMS Innovation Fund for Medical Sciences (CIFMS) (2018-I2M-1-004).

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Affiliations

  1. Center for Reproductive Medicine, Shandong University, Jinan, China

    Hai-Ning Liu

  2. Department of Reproductive Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, China

    Hai-Ning Liu, Xue-Qin Wang, Jing Gao, Ni Li & Yong-Yong Wang

  3. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China

    Hai-Ning Liu

  4. Reproductive and Genetic Center, National Research Institute for Family Planning, Beijing, China

    Hong-Fei Xia

  5. Graduate School, Peking Union Medical College, Beijing, China

    Hong-Fei Xia

  6. Department of Reproductive Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China

    Xiu-Ming Tang

Authors
  1. Hai-Ning Liu
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  2. Xiu-Ming Tang
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  3. Xue-Qin Wang
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  4. Jing Gao
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  5. Ni Li
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  6. Yong-Yong Wang
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  7. Hong-Fei Xia
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Correspondence to Hong-Fei Xia.

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Liu, HN., Tang, XM., Wang, XQ. et al. MiR-93 Inhibits Trophoblast Cell Proliferation and Promotes Cell Apoptosis by Targeting BCL2L2 in Recurrent Spontaneous Abortion. Reprod. Sci. 27, 152–162 (2020). https://doi.org/10.1007/s43032-019-00003-w

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  • DOI: https://doi.org/10.1007/s43032-019-00003-w

Keywords

  • miR-93
  • Recurrent spontaneous abortion
  • BCL2L2
  • Trophoblast cells