miR-141-3p affects apoptosis and migration of endometrial stromal cells by targeting KLF-12

Abstract

Endometriosis is an estrogen-dependent disease that is characterized by pelvic pain and infertility. MicroRNAs have been shown to implicate in the progression of endometriosis. In our study, we used real-time PCR to evaluate the expression of miR-141-3p in endometrial samples. In addition, western blot analysis was used to assess the expression of Krüppel-like factor 12 (KLF-12). The proliferation and migration of ectopic endometrial stromal cells (ESCs) were determined by MTT assay and Transwell assay, respectively. Cell apoptosis was evaluated using a Cell Death Detection ELISA Plus kit. The results showed that miR-141-3p and KLF-12 were significantly different in paired ectopic and eutopic endometrial samples. miR-141-3p overexpression significantly restrained the proliferation and migration and promoted the apoptosis of ectopic ESCs, whereas a decreased level of miR-141-3p was associated with opposite results. Furthermore, dual-luciferase reporter assay confirmed that KLF-12 was a novel target of miR-141-3p, while it also decreased the effects of miR-141-3p on the proliferation, apoptosis, and migration of ectopic ESCs. Our data suggested that enhanced expression of miR-141-3p suppressed the proliferation and migration of ectopic ESCs and promoted their apoptosis via targeting KLF-12. Our results may provide a novel potential therapeutic target for the treatment of endometriosis.

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Author information

Affiliations

Authors

Contributions

Yiwei Zhang and Juan Yan conceived and designed the study; Yiwei Zhang, Juan Yan, and Xiaowei Pan conducted experiments and collected the data; Yiwei Zhang and Juan Yan analyzed and interpreted the experiments results; Yiwei Zhang wrote the first draft of the manuscript; Yiwei Zhang, Juan Yan, and Xiaowei Pan revised the paper. All authors contributed to and approved the final manuscript.

Corresponding author

Correspondence to Yiwei Zhang.

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The hospital ethics committee approved this study.

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The authors declare that they have no conflict of interest.

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Highlights

1. miR-141-3p is obviously decreased in endometriosis.

2. KLF-12 is significantly upregulated in endometriosis.

3. Restoration of miR-141-3p expression in ectopic ESCs inhibits cellular proliferation and migration.

4. Restoration of miR-141-3p expression in ectopic ESCs induces the apoptosis in ectopic ESCs.

5. KLF-12 is directly regulated by miR-141-3p.

6. KLF-12 reverses the miR-141-3p-induced suppression of cell proliferation and migration.

7. KLF-12 inhibits the miR-141-3p-mediated induction of cell apoptosis.

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Zhang, Y., Yan, J. & Pan, X. miR-141-3p affects apoptosis and migration of endometrial stromal cells by targeting KLF-12. Pflugers Arch - Eur J Physiol 471, 1055–1063 (2019). https://doi.org/10.1007/s00424-019-02283-2

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Keywords

  • miR-141-3p
  • Proliferation
  • Apoptosis
  • Ectopic endometrial stromal cells
  • Krüppel-like factor 12