Open Access

MicroRNA‑202 inhibits endometrial stromal cell migration and invasion by suppressing the K‑Ras/Raf1/MEK/ERK signaling pathway

  • Authors:
    • Di Zhang
    • Ling Wang
    • Hua‑Lei Guo
    • Zi‑Wei Zhang
    • Chong Wang
    • Ri‑Cheng Chian
    • Zhi‑Fen Zhang
  • View Affiliations

  • Published online on: October 9, 2020     https://doi.org/10.3892/ijmm.2020.4749
  • Pages: 2078-2088
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The enhanced migratory ability of endometrial stromal cells (ESCs) is a key factor in the formation of functional endometrium‑like tissues outside the uterine cavity during endometriosis (EMS). Although accumulating evidence has suggested the importance of microRNAs (miRNAs) in the pathogenesis of EMS, the role of particular miRNAs in the invasiveness of ESCs remain poorly understood. In the present study, the function of miRNAs in the invasiveness of ESCs, along with the associated underlying mechanism involved, were investigated. Initially, the expression patterns of miRNAs in the ectopic and eutopic endometrium isolated from patients with EMS were analyzed using microarray. MicroRNA‑202‑5p (miR‑202) was selected for further study due to its previously reported suppressive effects on the invasion in various types of cancers. The expression of miR‑202 and K‑Ras in eutopic and ectopic endometrioma tissues were detected using reverse transcription‑quantitative PCR, immunohistochemistry and western blotting. The migration and invasion ability of ESCs was determined using wound healing and Transwell invasion assays, respectively. Compared with that from healthy individuals, miR‑202 expression was demonstrated to be lower in the eutopic endometrium from patients with EMS, which was even lower in ectopic endometrium. Functional experiments in primary ESCs revealed that enhanced miR‑202 expression suppressed the cell invasion and migration abilities, which was also accompanied with increased E‑cadherin and reduced N‑cadherin expression in ESCs, suggesting its potentially suppressive role in epithelial‑mesenchymal transition. K‑Ras is a well‑known regulator of the ERK signaling pathway that was shown to be directly targeted and negatively regulated by miR‑202. In addition, K‑Ras expression was found to be upregulated in the ectopic endometrium, where it correlated negatively with that of miR‑202. Knocking down K‑Ras expression mimicked the anti‑invasive effects of miR‑202 overexpression on ESCs, whilst K‑Ras overexpression attenuated the inhibitory role of miR‑202 overexpression in ESC invasion. The K‑Ras/Raf1/MEK/ERK signaling pathway was also blocked by miR‑202 overexpression. These findings suggested that miR‑202 inhibited ESC migration and invasion by inhibiting the K‑Ras/Raf1/MEK/ERK signaling pathway, rendering miR‑202 a candidate for being a therapeutic target for EMS.
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December-2020
Volume 46 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhang D, Wang L, Guo HL, Zhang ZW, Wang C, Chian RC and Zhang ZF: MicroRNA‑202 inhibits endometrial stromal cell migration and invasion by suppressing the K‑Ras/Raf1/MEK/ERK signaling pathway. Int J Mol Med 46: 2078-2088, 2020
APA
Zhang, D., Wang, L., Guo, H., Zhang, Z., Wang, C., Chian, R., & Zhang, Z. (2020). MicroRNA‑202 inhibits endometrial stromal cell migration and invasion by suppressing the K‑Ras/Raf1/MEK/ERK signaling pathway. International Journal of Molecular Medicine, 46, 2078-2088. https://doi.org/10.3892/ijmm.2020.4749
MLA
Zhang, D., Wang, L., Guo, H., Zhang, Z., Wang, C., Chian, R., Zhang, Z."MicroRNA‑202 inhibits endometrial stromal cell migration and invasion by suppressing the K‑Ras/Raf1/MEK/ERK signaling pathway". International Journal of Molecular Medicine 46.6 (2020): 2078-2088.
Chicago
Zhang, D., Wang, L., Guo, H., Zhang, Z., Wang, C., Chian, R., Zhang, Z."MicroRNA‑202 inhibits endometrial stromal cell migration and invasion by suppressing the K‑Ras/Raf1/MEK/ERK signaling pathway". International Journal of Molecular Medicine 46, no. 6 (2020): 2078-2088. https://doi.org/10.3892/ijmm.2020.4749